Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :1.6942617
The protein encoded by the 5 cyclin gene of this oncogenic herpesvirus was found to have an apparent molecular size of 29 kDa in transformed cells . 5 Cyclin protein was found to be associated with cdk 6 , a cellular cyclin dependent kinase known to interact with cellular type D cyclins . cdk6 / v cyclin complexes strongly phosphorylated Rb fusion protein and histone H 1 as substrates in vitro . 1.6942617^^^ Thus , 5 cyclin resembles cellular type D cyclins in primary sequence , in its association with cdk 6 , by its ability to activate protein kinase activity , and by the presence of functional cyclin box sequences . 5 Cyclin exhibited a selective preference for association with cdk 6 over other cyclin dependent kinases and a high level of kinase activation . 1.2802852^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.50613707
Furthermore , temporal alterations in the association of PCNA with p 21 and with CDK 6 were observed . 0.50613707^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.77087814
KSHV 5 cyclin protein was found to associate predominantly with cdk 6 , a cellular cyclin dependent kinase known to interact with cellular type D cyclins and HVS 5 cyclin . 0.77087814^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.51423903
Furthermore , cyclin D 3 immunoprecipitated fron as associated with cdk 6 , and the cyclin D3 / cdk6 complex was able to phosphorylate recombinant retinoblastoma protein in vitro . 0.51423903^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :1.0603586
These results suggest that EC 27 can function as a multifunctional cyclin : when associated with cdc 2 , it exhibits cyclin B like activity ; when associated with cdk 6 , the complex possesses cyclin D like activity and binds PCNA . 1.0603586^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.94382006
CONCLUSIONS : Although many critical interactions between cyclin A and CDK 2 would be conserved in a 5 cyclin CDK 2 complex , some appear sterically or electrostatically unfavorable due to shifts in the backbone conformation or sidechain differences and may contribute to 5 cyclin selectivity for CDK 6 . 0.94382006^^^ A virus encoded cyclin ( 5 cyclin ) from herpesvirus saimiri has been shown to exhibit highest sequence homology to type D cyclins and specifically activates CDK 6 of host cells to a very high degree . 0.76075468^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.56143773
This is in contrast to uninfected T cells , where cyclin D 2 associates only with cdk 6 . 0.56143773^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.62609405
In highly expressing BC 3 cells the cyclin is complexed with cdk 6 , cdk 4 , cdk 2 , and cdk 5 under both latent and lytic conditions , although subtle changes in the level of cdk association are seen after induction of the lytic cycle . 0.62609405^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.62475308
Here we present the 2 . 9 A crystal structure of the inactive ternary complex between Cdk 6 , the INK 4 inhibitor p 18 ( INK4c ) , and a D type viral cyclin . 0.62475308^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :1.2176548
In an anchorage minus G ( 1 ) arrested rat fibroblast , only Cdk 6 D3 retains kinase activity due mainly to its ability to evade inhibition by p 27 ( KIP 1 ) and p 21 ( CIP 1 ) with a resemblance to viral cyclin bound Cdk 6 . 1.2176548^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.91678587
Low levels of cyclin D and nonfunctional Rb protein affect cdk 6 association with cyclin dependent kinase inhibitor p 27 ( Kip 1 ) . p 27 ( Kip 1 ) associates with cyclin / cdk complexes and inhibiting cdk activity , and overexpression of p 27 ( Kip 1 ) induces G 1 arrest . 0.91678587^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.87872941
A striking difference between K cyclin and mammalian cyclins is that K cyclin binding to cdk 6 can substantially activate the catalytic activity of the complex without the requirement for cyclin H / cdk7 phosphorylation of the cdk T loop ; this phosphorylation is obligatory for endogenous cyclin / cdk activity . 0.87872941^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.72771041
An activated complex of human CDK 6 with a viral cyclin from herpesvirus saimiri was purified to homogeneity and crystallized using polyethylene glycol 3350 as precipitant . 0.72771041^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.6352272
This KSHV cyclin activates CDK 6 , alters its substrate specificity , and renders CDK 6 insensitive to inhibition by the cdk inhibitor p 16 ( INK4a ) . 0.6352272^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.80631237
K cyclin activates cellular cyclin dependent kinases ( CDK ) 4 and 6 , generating enzymes with a substrate selectivity deviant from CDK 4 and CDK 6 activated by D type cyclins , suggesting different biochemical and biological functions . 0.80631237^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In addition , six novel targets were detected : cyclin D 1 ( CCND 1 ) , cell division protein kinase 6 , collagen 8 alpha 1 subunit , CD 59 glycoprotein precursor , integrin beta 8 , and interleukin 6 precursor IFN beta 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Moreover , D type cyclin dependent kinase activity specifically activates the E2F 1 promoter by relieving E2F mediated repression but is inhibited by coexpression of the cdk 4 and cdk 6 inhibitor p 16 ( CDKN 2 , MTS 1 , INK 4 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors . p16INK4a and p15INK4b are cell cycle regulators that specifically bind to and inhibit the cyclin D dependent kinases , cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
One probable pathway for this growth inhibition is through the TGF beta mediated up regulation of the cyclin dependent kinase ( CDK ) inhibitor p15INK4B , which specifically inhibits the enzymatic activities of CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We have explored the interaction of p 21 with the currently known Cdks . p 21 effectively inhibits Cdk 2 , Cdk 3 , Cdk 4 , and Cdk 6 kinases ( Ki 0 . 5 15 nM ) but is much less effective toward Cdc2 / cyclin B ( Ki approximately 400 nM ) and Cdk5 / p35 ( Ki > 2 microM ) , and does not associate with Cdk7 / cyclin H . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The point in G 1 at which cells irrevocably commit to DNA synthesis is controlled by protein complexes consisting of cyclin dependent kinases ( CDK 4 or CDK 6 ) and cyclins ( D 1 , D 2 or D 3 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
G 1 progression in mammalian cells requires the activity of the cyclin D dependent kinases Cdk 4 and / or Cdk 6 and the cyclin E dependent kinase Cdk 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Progression through the G 1 phase of the cell cycle is regulated in part by the D type cyclin dependent kinases , cdk 4 and cdk 6 . ^^^ Like human p16INK4a , mouse p16INK4a binds specifically to cdk 4 and cdk 6 in vitro and inhibits the phosphorylation of the retinoblastoma protein , pRb , by each of these cyclin D dependent kinases . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
These cx 43 induced effects were coupled with a decreased expression of specific cell cycle regulatory genes critical to cell cycle progression in nonneoplastic cells including cyclin A , D 1 , D 2 , and the cyclin dependent kinases ( CDK ) 5 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The tandemly linked p16INK4aMTS1 and p15INK4b / MTS2 genes on chromosome 9 , band p 21 encode proteins that function as specific inhibitors of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Novel INK 4 proteins , p 19 and p 18 , are specific inhibitors of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^ Two novel members of the mouse INK 4 gene family , p 19 and p 18 , that specifically inhibit the kinase activities of CDK 4 and CDK 6 , but do not affect those of cyclin E CDK 2 , cyclin A CDK 2 , or cyclin B CDC 2 , were isolated . ^^^ Like the previously described human INK 4 polypeptides , p16INK4a / MTS1 and p15INK4b / MTS2 , mouse p 19 and p 18 are primarily composed of tandemly repeated ankyrin motifs , each ca . 32 amino acids in length , p 19 and p 18 bind directly to CDK 4 and CDK 6 , whether untethered or in complexes with D cyclins , and can inhibit the activity of cyclin D bound cyclin dependent kinases ( CDKs ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The G1 / S checkpoint is mainly dictated by the kinase activities of the cyclin D CDK 4 and / or cyclin D CDK 6 complex and the cyclin E CDK 2 complex . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
D type cyclins form active complexes with Cdk 4 or Cdk 6 earlier than E type cyclin does with Cdk 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Regulation of synthesis and activity of the PLSTIRE protein ( cyclin dependent kinase 6 ( cdk 6 ) ) , a major cyclin D associated cdk 4 homologue in normal human T lymphocytes . ^^^ The PLSTIRE protein ( cyclin dependent kinase 6 ( cdk 6 ) ) , which shares extensive sequence homology ( approximately 70 % ) with cdk 4 , was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12 , 13 dibutyrate and ionomycin ( PDB / I ) or PHA . ^^^ Thus , increased accumulation of the protein and its activity begin before IL 2 / IL 2 receptor interaction , suggesting that the cdk 6 cyclin D 2 complex might be involved in acquisition of the competent state in human T lymphocytes . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
D type cyclins , in association with the cyclin dependent kinases Cdk 4 or Cdk 6 , regulate events in the G 1 phase of the cell cycle and may contribute to the phosphorylation of the retinoblastoma gene product ( Rb ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclins D 1 , D 2 and D 3 preferentially associate with two closely related members of the cyclin dependent kinase family , Cdk 4 and Cdk 6 and the various complexes are each capable of phosphorylating the retinoblastoma gene product ( pRb ) , at least in vitro . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Relatively high amounts of PCNA were also found associated with cyclins D 2 and D 3 , the major cyclin partners of cdk 6 in T cells . ^^^ Both normal and transformed T cells contained PCNA in association with cdk 2 , cdk 4 , cdk 5 , and cdk 6 , with the amount of PCNA associated with these molecules increasing in the order listed . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The D type cyclin dependent kinases , CDK 4 and CDK 6 , have been strongly implicated in the control of G 1 progression and the phosphorylation of the retinoblastoma protein , pRb . ^^^ The formation of complexes and enzymatic activity of cyclin D CDK 4 and cyclin D CDK 6 kinases is negatively regulated by p16INK4 ( MTS1 / CDK4I / CDKN2 ) via its specific interaction with CDK 4 and CDK 6 catalytic subunits . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The D type cyclin dependent kinases CDK 4 and CDK 6 are complexed with many small cellular proteins ( p 14 , p 15 , p 16 , p 18 , and p 20 ) . ^^^ By use of a yeast interaction screen to search for CDK 6 interacting proteins , we have also identified an 18 kD human protein , p 18 , that is a homolog of the cyclin D CDK 4 inhibitors p 16 ( INK4A / MTS1 ) and p 14 ( MTS2 / INK4B ) . ^^^ Recombinant p 18 inhibits the kinase activity of cyclin D CDK 6 . ^^^ Distinct from the p21 / p27 family of CDK inhibitors that form ternary complexes with cyclin CDKs , only binary complexes of p 14 , p 16 , and p 18 were found in association with CDK 4 and / or CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In this study we have surveyed by immunoblotting the protein levels of Cyclin D 1 , D 2 , D 3 and their catalytic partners , Cdk 4 and Cdk 6 in normal and transformed human cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Identification of G 1 kinase activity for cdk 6 , a novel cyclin D partner . ^^^ Here , we show that the human PLSTIRE gene product is a novel cyclin dependent kinase , cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
CDK 6 ( PLSTIRE ) and CDK 4 ( PSK J 3 ) are a distinct subset of the cyclin dependent kinases that associate with cyclin D 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The INK4a ( MTS 1 , CDKN 2 ) gene encodes an inhibitor ( p16INK4a ) of the cyclin D dependent kinases CDK 4 and CDK 6 that blocks them from phosphorylating the retinoblastoma protein ( pRB ) and prevents exit from the G 1 phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Progression through the G 1 phase of the cell cycle is dependent on the activity of holoenzymes formed between D type cyclins and their catalytic partners , the cyclin dependent kinases cdk 4 and cdk 6 . p16INK4a , p15INK4b , and p18INK4c , a group of structurally related proteins , function as specific inhibitors of the cyclin D dependent kinases and are likely to play physiologic roles as specific regulators of these kinases in vivo . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 ( CDK 4 ) and CDK 6 and control cellular proliferation by preventing entry into the S phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Biochemical studies suggest that p16INK4 mediates its effects by specifically inhibiting the G 1 cyclin dependent kinases CDK 4 and CDK 6 , thereby regulating the progression through G 1 into S phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The cyclin D 1 protein was able to associate with the cell cycle dependent kinases , cdk 4 and cdk 6 , but not always with proliferating cell nuclear antigen in selected cell lines tested , representing a novel finding . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The regulation of the D type cyclin dependent kinase ( CDK 4 and CDK 6 ) activity appears to be the key step in the progression of eukaryotic cells through the G 1 cell cycle phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The remaining two mutations , a G to W mutation at position 101 ( Gl01W ) and V126D , both of which are associated with familial melanoma , were found to be temperature sensitive for binding to Cdk 4 and Cdk 6 in vitro , for inhibiting cyclin D 1 Cdk4 in a reconstituted pRb kinase assay , and for increasing the proportion of G 1 phase cells following transfection . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Relative mRNA expression levels were assessed using a rapid and sensitive Reverse Transcriptase Polymerase Chain Reaction ( RT PCR ) assay called the `` Primer dropping ' ' method . p16INK4 , a specific inhibitor of the cyclin D associated kinases CDK 4 and CDK 6 , was , in addition to p 21 and cyclin D 1 , overexpressed in higher passage cells , while the abundance of the D type kinase mRNAs remained relatively constant . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Tyrosine kinase inhibitor herbimycin A reduces the stability of cyclin dependent kinase Cdk 6 protein in T cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Recent studies have identified different CDK inhibitory genes ( CDKis ) , and two of them , p16ink4a / MTS1 / CDKN2 and p15ink4b / MTS2 are both mapped to chromosome 9p21 and inhibit cyclin D CDK 4 and CDK 6 complexes . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In contrast to p 21 and p 27 whose interaction with CDK subunits is dependent on or stimulated by the cyclin subunit , the interaction of p 19 and p 18 with CDK 6 is hindered by the cyclin protein . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The G 1 associated cyclin D 1 was not expressed at any stage of the anti Ig + IL 4 induced B cell cycle . cdk 2 , cdk 4 , and cdk 6 were induced during G 1 , whereas cell division cycle 2 ( cdc 2 ) was induced concomitantly with S phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
One of these genes , cyclin D 1 , is expressed in early G 1 phase , and its protein product , together with the cyclin dependent kinases CDK 4 and CDK 6 , mediates the phosphorylation and functional inactivation of the retinoblastoma protein ( pRb ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Overexpression of its product , p 16 , has been shown to block the transition through the G1 / S phase of the cell cycle in a pRb dependent fashion by inhibiting the cyclin D dependent kinases cdk 4 and cdk 6 . ^^^ RESULTS : We have identified a 20 residue synthetic peptide corresponding to amino acids 84 103 of p 16 that interacts with cdk 4 and cdk 6 , and inhibits the in vitro phosphorylation of pRb mediated by cdk 4 cyclin D 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In vitro and in nonproliferating cells , p 27 associates with and inhibits cyclin / cycin dependent kinase ( CDK ) holoenzymes containing either CDK 4 , CDK 6 , or CDK 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In JKB 2 cells , cyclin dependent kinase ( CDK ) 4 and CDK 6 formed complexes with cyclin D , due to the lack of p 16 , triggering phosphorylation of retinoblastoma protein ( pRB ) and continuous cell proliferation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Recently , two cell cycle regulators that inhibit the cyclin D 1 associated kinases cdk 4 and cdk 6 have been identified : p 16 and p 15 , the products of the INK4A ( also known as CDKN 2 , MTS 1 ) and INK4B ( also known as MTS 2 ) putative tumor suppressor genes located on 9p21 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The cyclin D dependent kinases CDK 4 and CDK 6 trigger phosphorylation of the retinoblastoma protein ( RB ) late in G 1 phase , helping to cancel its growth suppressive function and thereby facilitating S phase entry . ^^^ Although specific inhibition of cyclin D dependent kinase activity in vivo can prevent cells from entering S phase , it does not affect S phase entry in cells lacking functional RB , implying that RB may be the only substrate of CDK 4 and CDK 6 whose phosphorylation is necessary for G 1 exit . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The first group , including p16Ink4a , p15Ink4b , p18Ink4c and p19Ink4d , is specific for the G 1 CDKs , CDK 4 and CDK 6 , inhibiting the kinase activity of cyclin D / CDK4 CDK 6 complexes on pRb . p16Ink4a , down regulated by pRb , inhibits G 1 CDKs by competition with cyclin D ; p15Ink4b , the synthesis of which is induced by TGF beta , seems to be a mediator of TGF beta mediated cell cycle arrest . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
An obvious focus is the so called restriction point in late G 1 , and current evidence suggests that this is in part determined by the phosphorylation of the retinoblastoma protein ( Rb ) by the cyclin D dependent kinases , CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
However , like vertebrate cdk 4 and cdk 6 , Drosophila cdk4 / 6 binds also to a D type cyclin according to the results of two hybrid experiments in yeast . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The transition from G 1 to S phase is dependent on D cyclins in complex with cdk 4 or cdk 6 and cyclin E complexed with cdk 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We studied several cyclin dependent kinases ( cdk 1 , cdk 2 , cdk 4 , cdk 6 ) and cyclins ( cyclin A , cyclin B 1 , cyclin D 3 and cyclin E ) . ^^^ Cdk 6 , which was highly correlated to PCNA , was also higher in T cell ALL . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The SK 29 MEL 1 cell line harboring an R24C mutation in Cdk 4 expressed wild type pRb and overabundant p 16 , the latter preventing endogenous Cdk 6 but not Cdk 4 from associating with cyclin D 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
On the other hand , there was no significant difference in expression of proteins such as Rb , p 16 , cdk 4 , cdk 6 , cyclin A and cyclin D 1 between the normal and immortalized human fibroblasts . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Overexpression of p 16 in these cells results in sequestering of cdk 4 and cdk 6 , rendering cyclin D1 / cdk complexes inactive . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Although the abundance of cyclin D 1 , Cdk 4 , and Cdk 6 did not decrease cyclin D 1 associated kinase activity was reduced by approximately 50 % at 9 18 h . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 was dominant among the D type cyclins , formed abundant complexes with cyclin dependent kinase ( Cdk ) Cdk 4 rather than Cdk 6 , and the immunoprecipitated cyclin D1 / Cdk4 holoenzyme was active as a pRB kinase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In the GCT cell lines in which cyclin D 2 was highly expressed , cyclin D 2 was in complex with its expected catalytic partners ( Cdk 4 and Cdk 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
SNAP inhibited the activity of cyclin dependent kinase 2 ( Cdk 2 ) and phosphorylation of the retinoblastoma protein , both of which usually increased from about 9 h , whereas it did not inhibit the activities of cyclin D associated kinase ( s ) , Cdk 4 , and Cdk 6 , which normally increased from 0 3 h . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
OBJECTIVE : The recently cloned gene p 16 ( MST 1 ) has been identified as a putative tumor suppressor gene that binds to CDK 4 and CDK 6 ( cyclin dependent kinases ) , preventing their interaction with cyclin D 1 and thereby preventing cell cycle progression at the G 1 stage . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 in cooperation with its major catalytic partners , cyclin dependent kinases cdk 4 and cdk 6 , facilitates progression through the G 1 phase of the eukaryotic cell cycle , in part through phosphorylation of the retinoblastoma protein . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
These stimulations were associated with a decrease in cyclin dependent kinase ( cdk ) 2 level , whereas cdk 4 and cdk 6 remained unchanged . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression of D type G 1 cyclins and their assembly with their catalytic partners , the cyclin dependent kinases 4 and 6 ( CDK 4 and CDK 6 ) , into active holoenzyme complexes are regulated by growth factor induced signals . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 are not down regulated in L 929 cells after addition of glucocorticoids , and the abundance of cyclin D / Cdk4 complexes does not change . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The cyclin encoded by Kaposi ' s sarcoma associated herpesvirus stimulates cdk 6 to phosphorylate the retinoblastoma protein and histone H 1 . ^^^ This may have important physiological consequences in that the kinase activity triggered by this viral cyclin may abrogate cell cycle checkpoints in addition to those targeted by cellular cyclin D cdk 6 kinase . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
GR activation in U2OS cells represses expression of the cyclin dependent kinases ( CDKs ) CDK 4 and CDK 6 as well as their regulatory partner , cyclin D 3 , leading to hypophosphorylation of the retinoblastoma protein ( Rb ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
To elucidate the roles of cyclin dependent kinase 6 ( cdk 6 ) in T cells , we examined its intracellular localization , kinase activity , and associated proteins in the Jurkat T lymphoblastoid cell line . ^^^ Jurkat cells had a high level of cdk 6 , which was associated with cyclin D 3 , but not cyclin D 2 , the member of the cyclin D family . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Effects of exogenous p16INK4a on growth of cells with various status of cell cycle regulators . p16INK4a , a protein that inhibits cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , is deficient in many human cancers and in established lines of tumor cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The cyclin D 2 associated kinase activity was largely inhibited by Cdk 2 specific inhibitors and could phosphorylate histone H 1 , a substrate for Cdk 2 but not for Cdk 4 and Cdk 6 . ^^^ In contrast , Cdk 4 and Cdk 6 were predominantly responsible for cyclin D 1 associated kinase activity as previously reported . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In cells of higher eukaryotes , cyclin D dependent kinases Cdk 4 and Cdk 6 and , possibly , cyclin E dependent Cdk 2 positively regulate the G 1 to S phase transition , by phosphorylating the retinoblastoma protein ( pRb ) , thereby releasing E2F transcription factors that control S phase genes . ^^^ We demonstrate that ectopic expression of cyclin E , but not cyclin D 1 , can override G 1 arrest imposed by either the p16INK4a Cdk inhibitor specific for Cdk 4 and Cdk 6 or a novel phosphorylation deficient mutant pRb . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Mammalian D type cyclins are differentially expressed during the first gap phase ( G 1 ) of the cell cycle in various cell types , and function as regulatory subunits of cyclin dependent kinases ( cdks ) , cdk 4 and cdk 6 , to form holoenzymes whose activities are both necessary and rate limiting for G 1 progression . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Analysis of expression of genes regulating Rb phosphorylation revealed that activin A suppressed cyclin D 2 , the sole D type cyclin gene expressed in the hybridoma cells , and activated p21CIP1 / WAF1 but had no effect on expression of cyclin dependent kinases ( CDK 2 , CDK 4 , CDK 6 ) and other CDK inhibitors ( p27KIP1 , p16INK4a , p15INK4b ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of BIP with cyclins / CDKs and E2F antisera indicated association with cdc 2 , cdk 2 , cdk 4 , cyclin B , cyclin D , cyclin A and E2F 4 but not with cdk 3 , cdk 5 , cdk 6 , E2F 1 , E2F 2 , E2F 3 , E2F 5 and cyclin E . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Assay for activity of mammalian cyclin D dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The 1p35 p 31 region contains an excellent candidate tumor suppressor gene , p 18 , whose product is a cell cycle regulator that inhibits the cyclin D 1 associated kinase CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Whereas the level of expression and activity of cyclin D 1 and its associated kinase , cdk 6 , was modest in tumor cells , both cyclin A and E , and their kinase partners , cdk 2 and cdk 4 , were highly expressed and exhibited significant kinase activity . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Reverse transcription polymerase chain reaction ( RT PCR ) analysis indicated that TGF beta 1 mediated G 1 arrest correlated with the down regulation of cdk 4 , cdk 6 and cyclin D 2 , and that abrogation of TGF beta 1 mediated G 1 arrest by GM CSF correlated with the constitutive over expression of cyclin D 2 and cdk 6 but not cdk 4 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In mammalian cells , the G1 / S specific CDK activities are composed of complexes between D type cyclins and either CDK 4 or CDK 6 and between cyclin E ( and possibly cyclin A ) and CDK 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
To test this hypothesis , we used the RNA alphavirus Sindbis to express three known cyclin dependent kinase inhibitors ( CKIs ) , p 16 ( ink 4 ) , p 21 ( waf / cip ) , and p 27 ( kip 1 ) , and dominant negative mutant forms of four known G 1 cyclin dependent kinases ( CDKs ) , Cdk 2 , Cdk 3 , Cdk 4 , and Cdk 6 , in primary cultured rat superior cervical ganglion sympathetic neurons . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The passage of mammalian cells through the restriction point into the S phase of the cell cycle is regulated by the activities of Cdk 4 and Cdk 6 complexed with the D type cyclins and by cyclin E / Cdk2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In situ hybridization of mouse embryo sections demonstrated expression of mRNAs encoding two polypeptide inhibitors ( p18INK4c and p19INK4d ) of cyclin D dependent kinase ( CDK ) 4 and CDK 6 in the central nervous system . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The p16 / MTS1 / CDKN2 gene on human chromosome band 9p21 encodes two unrelated proteins : p16INK4a , a specific inhibitor of the cyclin D dependent kinases CKD 4 and CDK 6 , and the structurally unrelated p19ARF protein that arrests cell growth in G1 / S and also in G2 / M . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The Rb cyclin D pathway was analyzed by studying the pRb protein , the p16MTS1 gene , cyclin D 1 , cyclin D 3 , p27Kip1 , cdk 4 , and cdk 6 proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Hence , both the cyclin D 1 and D 3 as well as CDK 4 and CDK 6 subunits can confer substrate specificity on the overall cyclin D CDK complex . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In mammalian cells , the G 1 phase progression is controlled by the serial activation of several cyclin dependent kinases ( Cdks ) , starting with Cdk 4 and Cdk 6 . ^^^ The suppression of Tax synthesis , however , resulted in a significant reduction of the Cdk 4 and Cdk 6 activities but did not influence the expression of Cdk 4 , Cdk 6 , or cognate D type cyclin proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D / CDK4 and CDK 6 may conceivably also be activated by Myc , but the circumstances in which this occurs remain to be explored . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We have previously shown that a 20 amino acid peptide derived from the third ankyrin like repeat of the p16CDKN2 / INK4a ( p 16 ) tumour suppressor protein ( residues 84 103 of the human p 16 protein ) can bind to cdk 4 and cdk 6 and inhibit cdk 4 cyclin D 1 kinase activity in vitro as well as block cell cycle progression through G 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
These data suggest that even though there are cdk6 / cyclin D complexes detectable in both the cytoplasm and nucleus , only the cdk 6 that is in the nucleus is active . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 3 , a major component of the cyclin dependent kinase ( CDK ) activity required for pRb phosphorylation , was completely abrogated by MPA treatment of T cells activated by interleukin 2 ( IL 2 ) and leucoagglutinin ( PHA L ) , whereas the expression of cyclin D 2 , CDK 6 , and CDK 4 was more mildly attenuated . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Following silymarin treatment of cells , an incremental binding of Cip1 / p21 with CDK 2 and CDK 6 paralleled a significant decrease in CDK 2 , CDK 6 , cyclin D 1 , and cyclin E associated kinase activity with no change in CDK 2 and CDK 6 expression but a decrease in G 1 cyclins D 1 and E . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 2 was also found to be associated with the cyclin dependent kinases CDK 2 and CDK 4 but not CDK 6 during growth arrest . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Sho saiko to arrested Mel ret cells in G 1 phase by decreasing the expression of cyclin dependent kinase ( cdk ) 4 and its homologue cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 , CDK 4 , and CDK 6 involved in G 1 phase control were significantly decreased under dexamethasone treatment whatever the level of stimulation of lymphocytes ( stimulated or unstimulated PBL ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blot analysis revealed that PDT results in an induction of the cyclin kinase inhibitor WAF1 / CIP1 / p21 , and a down regulation of cyclin D 1 and cyclin E , and their catalytic subunits cyclin dependent kinase ( cdk ) 2 and cdk 6 . ^^^ PDT also resulted in ( 1 ) an increase in the binding of cyclin D 1 and cdk 6 toward WAF1 / CIP1 / p21 , and ( 2 ) a decrease in the binding of cyclin D 1 toward cdk 2 and cdk 6 . ^^^ These data suggest that PDT mediated induction of WAF1 / CIP1 / p21 results in an imposition of artificial checkpoint at G 1 > S transition thereby resulting in an arrest of cells in G 0 G1 phase of the cell cycle through inhibition in the cdk 2 , cdk 6 , cyclin D 1 , and cyclin E . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The cyclin dependent kinase ( CDK ) inhibitor p 18 blocks progression of the cell cycle by associating with the cyclin D dependent kinases CDK 6 and CDK 4 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The protein levels of cyclin dependent kinase ( Cdk ) 2 , Cdk 4 and Cdk 6 are not altered in the resistant sublines . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The resulting growth inhibitory effect of HMBA was completely reversible and was analyzed in terms of percent cells in G 1 ; association of D type cyclins with cyclin dependent kinase ( cdk ) 4 and cdk 6 ; G 1 kinase activity ; association of retinoblastoma protein ( pRb ) and phosphorylated pRb with D type cyclins ; and association of p16INK4a , p15INK4b , and p27Kip1 with cdk 4 and cdk 6 . ^^^ The data suggest that HMBA induced growth inhibition is due to multifactorial mechanisms involving decreases in total cyclin D 1 and inhibition of cdk 4 and cdk 6 kinase activities through elevation of levels of cdk 4 and cdk 6 associated p27Kip1 and concomitant increases in hypophosphorylated pRb and stable cyclin D2 / pRb and cyclin D3 / pRb complexes that help maintain pRb in a functional state . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of cell lysates from untreated or TGF beta treated cultures showed no alterations in expression of CDK 2 , CDK 4 , CDK 6 or cyclin E in cell lines which were either sensitive ( HaCaT , HN 6 ) or refractory ( HN 12 , HN 30 ) to the growth inhibitory effects of TGF beta . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 expression was absent despite high levels of CDK 4 and CDK 6 , and the CKI p 27 was expressed in chondrocytes , osteoclasts , and at lower levels in osteoblasts . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In non tumorigenic mouse liver cells cyclin D 1 associated with CDK 6 , CDK 4 or CDK 2 to form binary ( cyclin D 1 CDK ) , tertiary ( cyclin D 1 CDK p27KIP1 ) or quaternary ( cyclin D 1 CDK p21WAF1 PCNA ) complexes . ^^^ Interestingly , CDK 6 kinase activity was dramatically elevated due to high levels of cyclin D 3 in association with CDK 6 . ^^^ In MNNG transformed cells select cyclin D 1 CDK6 CDI and cyclin D 1 CDK2 CDI protein complexes were altered but CDK 6 and CDK 4 kinase activity remained unaffected . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Taken together , our findings suggest that cyclin D 3 , cdk 6 , and p 27 play key roles in IL 2 , IL 4 , and IL 10 mediated human B cell proliferation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
INTRODUCTION : The purpose of this study was to determine whether the multiple tumor suppressor 2 ( MTS 2 ) gene , encoding an inhibitor ( p 15 ) of cyclin D dependent kinases 4 and 6 ( cdk 4 , cdk 6 ) , is deleted in head and neck squamous cell carcinomas ( HNSCC ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Furthermore , p 40 ( MO 15 ) only phosphorylated cdk 6 bound to cyclin D 3 , whereas Cak1p recognized monomeric cdk 6 and cdk 6 bound to cyclin D 1 , D 2 , or D 3 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Likewise , cyclin D is complexed with its catalytic partners CDK 4 and CDK 6 in senescent HDF , but it is not known whether these complexes are active . p21Sdi1 , Cip 1 , Waf 1 , a ubiquitous inhibitor of the activity of cyclin CDK complexes , increases progressively throughout the life span of HDF , but then declines again after the cells become senescent . ^^^ In contrast , p16Ink4a , which binds monomeric CDK 4 and CDK 6 thereby preventing their binding to cyclin D , is increased dramatically at the time of senescence and remains high for at least 2 mo . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
While the protein levels of cyclin D 1 , cyclin D 3 , CDK 4 , CDK 6 and CDK 2 were still detectable in adult atria , the protein levels of cyclin E , cyclin A , cyclin B , cdc 2 and PCNA were not detectable . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The mammalian D type cyclins D 1 , D 2 , and D 3 activate the cyclin dependent kinases CDK 4 and CDK 6 in G 1 and thereby promote the cell ' s commitment to enter S phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Structural basis for inhibition of the cyclin dependent kinase Cdk 6 by the tumour suppressor p16INK4a . ^^^ The structures of Cdk 6 bound to p16INK4a and to the related p19INK4d reveal that the INK 4 inhibitors bind next to the ATP binding site of the catalytic cleft , opposite where the activating cyclin subunit binds . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Crystal structure of the complex of the cyclin D dependent kinase Cdk 6 bound to the cell cycle inhibitor p19INK4d . ^^^ The crystal structure of the cyclin D dependent kinase Cdk 6 bound to the p 19 INK4d protein has been determined at 1 . 9 A resolution . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Corresponding to the inhibited cdk function , we demonstrate a low expression of cyclin D in mid G 1 determined by Western blot analysis , and cyclin D was greatly reduced in the immunocomplex recovered with antibody to cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
LCLs arrested in G0 / G1 by RA also showed a significant decrease in the protein levels of cyclins D 2 , D 3 and A , together with a reduction in the amount of cyclin D associated with CDK 4 and CDK 6 , probably accounting for the inhibition of the relative kinase activity . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The results showed that the cell lines expressed varying amounts of most cyclin and CDK ' s but only a few of the cell lines expressed cyclin D 1 and / or D 2 and some lacked expression of CDK 6 . ^^^ The mRNA expression differed for a few of the cell lines regarding cyclin D 2 and CDK 6 when in vitro and in vivo data were compared . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The tumour suppressor p 16 is a member of the INK 4 family of inhibi tors of the cyclin D dependent kinases , CDK 4 and CDK 6 , that are involved in the key growth control pathway of the eukaryotic cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Degradation of p 27 ( Kip ) cdk inhibitor triggered by Kaposi ' s sarcoma virus cyclin cdk 6 complex . ^^^ Complexes formed between the viral cyclin and the cyclin dependent kinase subunit , cdk 6 , can phosphorylate a wider range of substrates and are resistant to cdk inhibitory proteins . ^^^ We show here that the KSHV cyclin cdk 6 complex phosphorylates p 27 ( Kip ) on a C terminal threonine that is implicated in destabilization of this cdk inhibitor . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We demonstrate that binding of K cyclin to cdk 6 expands the substrate repertoire of this cdk to include a number of substrates phosphorylated by cyclin cdk 2 complexes but not cyclin D 1 cdk6 . ^^^ The extension of the substrate repertoire of cdk 6 by K cyclin is likely to contribute to the deregulation of cellular growth by this herpesvirus encoded cyclin . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
As expected , induction of p 16 ( INK4a ) results in a G 1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein ( pRb ) by the cyclin dependent kinases CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
P 4 pretreatment did not alter overall levels of cyclin D 1 , cdk 4 , or cdk 6 nor their associated kinase activities but instead inhibited the E 2 induced nuclear localization of cyclin D 1 to below the control level and , to a lesser extent , nuclear cdk 4 levels , with a consequent inhibition of pRb and p 107 phosphorylation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Furthermore , GGTI 298 has little effect on the expression levels of CDK 2 , CDK 4 , CDK 6 , cyclins D 1 and E , but decreases the levels of cyclin A . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
USA ; 95 : 6977 6982 , 1998 ) that silicon phthalocyanine ( Pc 4 ) PDT results in an induction of the cyclin kinase inhibitor WAF1 / CIP1 / p21 which , by inhibiting cyclins ( E and D 1 ) and cyclin dependent kinases ( cdk 2 and cdk 6 ) , results in a G0 / G1 phase arrest followed by apoptosis in human epidermoid carcinoma cells A 431 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Transcriptional activation by HHV 8 Vcyc depends on an E2F binding site in the cyclin A promoter , and cdk 6 kinase activity is required . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Hepatocyte growth factor releases mink epithelial cells from transforming growth factor beta 1 induced growth arrest by restoring Cdk 6 expression and cyclin E associated Cdk 2 activity . ^^^ While TGF beta treatment decreased the expression of Cdk 6 , this effect was counteracted by HGF , followed by partial restoration of cyclin D 2 associated kinase activity . ^^^ However , HGF reversed the TGF beta mediated decrease in Cdk 6 associated p 27 and cyclin D 2 associated Cdk 6 , suggesting that HGF modifies the TGF beta response at the level of G 1 cyclin complex formation . ^^^ Counteraction of TGF beta regulation of Cdk 6 by HGF may in turn affect the association of p 27 with Cdk 2 cyclin E complexes . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In these clones , binding of p 16 to cdk 4 and cdk 6 abrogated binding of cyclin D 1 , p 27 ( KIP 1 ) , and p 21 ( WAF1 / CIP1 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Further , CTLA 4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D 3 , cyclin dependent kinase ( cdk ) 4 , and cdk 6 when the T cells were stimulated with anti CD3 / CD28 and with anti CD 3 alone . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Here we report that in UV irradiated HeLa and A 2058 cells , p 16 bound Cdk 4 and Cdk 6 complexes with increased avidity and inhibited a cyclin D 3 Cdk4 complex normally activated in late S / early G 2 phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin A ( a regulatory subunit of cdk 2 ) markedly decreased , while cyclin D 1 , the major cdk 4 partner in fibroblasts , expressed at a slightly higher level and formed complexes with cdk 2 and cdk 6 in addition to cdk 4 . ^^^ Induction of p19ARF activated p 53 by increasing its stability , and allowed the expression of p21Cip1 , which bound to all of the cyclin D 1 cdk complexes ( cyclin D 1 cdk2 , cdk 4 , and cdk 6 ) thereby inhibiting their kinase activities . p19ARF formed complexes with several cellular proteins including mouse MDM 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression levels of cdk 2 , cdk 4 and cdk 6 were the same in 3T3 PCNA and NIH 3T3 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Myc regulates cyclin D Cdk 4 and Cdk 6 activity but affects cell cycle progression at multiple independent points . c myc is a cellular proto oncogene associated with a variety of human cancers and is strongly implicated in the control of cellular proliferation , programmed cell death , and differentiation . ^^^ The largest defect observed in c myc / cells is a 12 fold reduction in the activity of cyclin D 1 Cdk4 and Cdk 6 complexes during the G 0 to S transition . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Silibinin induced G 1 arrest was associated with a marked decrease in the kinase activity of cyclin dependent kinases ( CDKs ) and associated cyclins because of a highly significant decrease in cyclin D 1 , CDK 4 , and CDK 6 levels and an induction of Cip1 / p21 and Kip1 / p27 followed by their increased binding with CDK 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In mammals , cyclin D can assemble with CDK 4 and CDK 6 , but not with Cdc 2 , to form active complexes . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Over expression of CDK 2 , CDK 6 , CDC25A and cyclin A was confirmed in melanoma cell lines . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin / cyclin dependent kinase ( CDK ) complexes immunoprecipitated with p27Kip1 are differentially modified by DXM addition : ( a ) G 1 kinasic complexes ( cyclin D / CDK4 or CDK 6 ) associated with p27Kip1 are strongly decreased by DXM , ( b ) S phase complexes ( CDK2 / cyclin E and A ) remained stable or increased , and ( c ) the association of p27Kip1 with the phosphorylated forms of CDK 1 is increased by DXM . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The D type cyclins ( cyclin D 1 , D 2 , and D 3 ) promote cell cycle progression from G 1 to S phase by binding to and activating the cyclin dependent kinases Cdk 4 and Cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In addition , cyclin D1 / cyclin dependent kinase ( CDK ) complex formation increased in the transgenic mice and was correlated with elevated CDK 4 and CDK 6 kinase activities . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Accumulation of these cells at G 1 is not associated with major changes in expression level of cyclin dependent kinase ( cdk ) 2 , cdk 4 , and cdk 6 ; cyclin D 1 and cyclin E ; or p 16 , p 21 , p 27 , and p 57 after CPT treatment . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Immunohistochemical analysis of the D type cyclin dependent kinases Cdk 4 and Cdk 6 , using a series of monoclonal antibodies . ^^^ Cellular signal transduction cascades triggered by mitogenic or antiproliferative cues eventually converge on a biochemical mechanism centered around the retinoblastoma tumor suppressor ( pRb ) , the so called RB pathway that governs G 1 phase progression and guards the commitment to enter S phase . pRb , together with its immediate upstream regulators , the D type cyclins , their partner cyclin dependent kinases Cdk 4 and Cdk 6 , and the Cdk inhibitors , form a functional unit that is involved in major decisions about cellular fate , and whose components , including the proto oncogenic cyclin D dependent kinases , are commonly deregulated in many types of cancer . ^^^ Collectively , the antibodies described in this study provide the means for immunochemical analyses of the cyclin D dependent kinases in human and animal cells , and represent useful molecular tools that should help better understand the biological roles of Cdk 4 and Cdk 6 in normal cell cycle control , and their oncogenic activity in tumor cells . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
There was no effect on p 21 ( Cip 1 ) , cyclin D 2 , cdk 4 , and cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Our results point to some particularities of cell cycle regulation in two lymphoma sub types : 1 ) a low expression of cyclin D 3 and cdk 6 in mantle cell lymphomas and 2 ) a discrepancy between the high proliferative activity and the level of protein expression in Burkitt ' s lymphomas . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In many organisms , initiation and progression through the G ( 1 ) phase of the cell cycle requires the activity of G ( 1 ) specific cyclins ( cyclin D and cyclin E ) and their associated cyclin dependent kinases ( CDK 2 , CDK 4 , CDK 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The decrease in pRB phosphorylation correlated with inhibitor induced suppression of G ( 1 ) cyclin dependent kinases including CDK 2 , CDK 4 , and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Because G0 / G1 and G1 / S transitions are regulated in part by cyclin dependent kinase Cdk 6 , we investigated the possibility that a loss of activity of this kinase is implicated in the age related dysfunction of the cell cycle in its initial phases . ^^^ However , at least two other mechanisms might be incriminated in the loss of Cdk 6 activity : ( 1 ) a poor induction of the associated cyclin D 2 upon anti CD 3 stimulation and ( 2 ) a delayed downregulation of the Cdk inhibitor p 27 following cell activation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
However , both Cdk 4 and Cdk 6 are activated upon serum stimulation , and neither the amounts of Cdk 6 , Cdk 4 , cyclin D 1 , and cyclin dependent kinase inhibitors nor the activities or subcellular localization of Cdk 6 and Cdk 4 are significantly influenced by oncogenic stimulation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Analysis of cell cycle regulatory proteins demonstrated that As ( 2 ) O ( 3 ) ( 2 microM ) did not change the steady state levels of CDK 2 , CDK 4 , CDK 6 , cyclin D 1 , cyclin E and cyclin A , but decreased the protein levels of cdc 2 and cyclin B 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The p 16 ( INK4a ) tumor suppressor inhibits cyclin dependent kinases ( CDK 4 and CDK 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors includes four 15 to 19 kDa polypeptides ( p 16 ( INK4a ) , p 15 ( INK4b ) , p 18 ( INK4c ) , and p 19 ( INK4d ) ) that bind to CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In three patients with translocations between chromosomes 2 and 7 , the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3 . 6 kb upstream of the transcription start site of cyclin dependent kinase 6 ( CDK 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
To further investigate the differences between mitogen induced mouse hepatocyte proliferation and liver regeneration after PH , we have measured the expression of cyclin D 1 , cyclin D 3 , cyclin E , and cyclin A and of the cyclin dependent kinases CDK 2 , CDK 4 , and CDK 6 . ^^^ The expression of other proteins involved in cell cycle control , such as cyclin dependent kinases ( CDK 4 , CDK 2 , CDK 6 ) , was also analyzed . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Analysis of G ( 1 ) regulatory proteins demonstrated that protein levels of CDK 2 , CDK 4 , cyclin D 1 , and cyclin A were decreased in a time dependent manner , but not those of CDK 6 and cyclin E , by EB 1089 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
These differences correlated with the growth fraction for both the G 1 cyclins cdks ( r = 0 . 91 , 0 . 94 , 0 . 85 , 0 . 90 and 0 . 96 for cyclin D 1 , cyclin E , cdk 2 , cdk 4 and cdk 6 , respectively ) and the G2M cyclins cdks ( r = 0 . 96 , 0 . 97 and 0 . 93 for cyclins A , B and cdkl respectively ) . ^^^ Overexpression of other cyclins cdks were observed , from the 6th day on for cyclin D 1 , the 12th day for cdk 2 and cdk 4 , the 15th day for cdk 6 and the 20th day for cyclin E . ^^^ These increases persisted during tumoral progression and correlated with the growth fraction ( r = 0 . 85 , 0 . 94 , 0 . 93 , 0 . 96 , and 0 . 98 for cyclin D 1 , cyclin E , cdk 2 , cdk 4 and cdk 6 , respectively ) ( n = 20 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of cyclin D 1 immunoprecipitates indicated complex formation with both cyclin dependent kinase 4 ( Cdk 4 ) and cyclin dependent kinase 6 ( Cdk 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Analysis of G 1 regulatory proteins demonstrated that the protein levels of cyclin dependent kinase ( CDK ) 2 , CDK 4 , CDK 6 and cyclin E were decreased after treatment with lovastatin ( 10 microM ) in a time dependent manner , but not cyclin D 1 . ^^^ In addition , lovastatin increased the protein level of the cyclin dependent kinase inhibitor ( CDKI ) , p 27 , and markedly enhanced the binding of p 27 with CDK 2 and CDK 4 more than CDK 6 after 24 h exposure . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Compatible with the effects on the cell cycle , treatment with mAb ID 5 decreased levels of cyclin dependent kinase ( CDK ) 2 , cyclin E , and CDK 6 proteins and reduced cyclin E CDK 2 associated kinase activity ; mAb HD 5 treated cells had increased p27Kip1 expression and an increased association of p27Kip1 with CDK 2 . ^^^ In contrast , treatment with heregulin increased protein levels of CDK 2 , CDK 6 , CDC 2 , and cyclin B 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The inhibition of cyclin D / CDK4 , 6 kinase activity corresponded to a loss of cyclin D 1 protein and a failure of CDK 4 and CDK 6 to translocate to the nucleus . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We analysed p 16 gene alteration and p 16 , cyclin dependent kinase 4 ( CDK 4 ) , CDK 6 , cyclin D 1 , cyclin D 2 , cyclin D 3 and retinoblastoma protein ( pRb ) expression in ten normal endometriums ( PE ) , 18 endometrial hyperplasias ( EH ) and 35 endometrial cancers ( EC ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The concentrations of most cyclin dependent kinases ( Cdk 2 , Cdk 4 , and Cdk 6 ) , however , were unchanged by PMA treatment . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The molecular events that lead to melanoma cell autonomous growth are not well defined , but are likely to include sustained activity of cyclin dependent kinases ( CDK 2 , CDK 4 and CDK 6 ) as a result of loss of CDK inhibitors ( such as p16INK4a and possibly p27KIP1 ) , and persistent upregulation of several cyclins ( cyclin D 1 , cyclin A and cyclin E ) , the positive regulators of CDKs . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
A tumor suppressor gene , p 16 ( INK 4 ) , which is deleted or mutated in tumors , regulates cell cycle progression through a G ( 1 ) S restriction point by inhibiting CDK 4 ( CDK 6 ) / cyclin D mediated phosphorylation of pRb . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
D 1 , p16INK4a and pRb expression in resectable non small cell lung cancer . p 21 ( p21WAF1 / CIP1 ) is involved in cell cycle regulation , as an inhibitor of cyclin dependent kinases ( CDK 2 , CDK 4 and CDK 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
E6 / E7 expression in mouse epidermis is correlated with increased levels of the p 53 , p 21 , p 27 , cdk 2 , cdk 4 , cdk 6 , cyclin D 1 and cyclin E regulatory proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
As p 16 ( INK4A ) increased in cdk 4 and cdk 6 complexes , there was a loss of cyclin D 1 binding . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Forty eight h after SCF withdrawal and Epo stimulation , there was strong inhibition of cyclin dependent kinase ( cdk ) 4 and cdk 6 activities , associated with an increase in the binding of p 27 and p 15 to cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blot analysis demonstrated that treatment with As2O3 ( 2 microM ) for 72 h did not change the steady state levels of CDK 2 , CDK 4 , cyclin D 1 , cyclin E , and cyclin B 1 but decreased the levels of CDK 6 , cdc 2 , and cyclin A . ^^^ In addition , As2O3 markedly enhanced the binding of p 21 with CDK 6 , cdc 2 , cyclin E , and cyclin A compared with untreated control cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Entry of quiescent cells into the cell cycle is driven by the cyclin D dependent kinases Cdk 4 and Cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Mitogen dependent , cyclin D dependent kinases ( cdk 4 and cdk 6 ) phosphorylate the retinoblastoma ( Rb ) tumor suppressor protein , helping to cancel its growth inhibitory effects and enabling E2F transcription factors to activate genes required for entry into the DNA synthetic phase ( S ) of the cell division cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The oncogenic role of reduced , but not absent , levels of p27KIP1 is supported by recent studies in murine models and evidence that this protein not only inhibits the activity of complexes containing CDK 2 and cyclin E , but also promotes the assembly and catalytic activity of CDK 4 or CDK 6 in complexes with cyclin D . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We did not observe consistent changes in protein levels of cyclin D , cyclin E , CDK 4 , CDK 6 , CDK 2 , p 27 ( Kip 1 ) , p 16 ( INK4a ) , or RNA levels of p 15 ( INK4b ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
As shown by immunoblot analysis , EGCG treatment of the cells resulted in significant dose and time dependent ( 1 ) upregulation of the protein expression of WAF1 / p21 , KIP1 / p27 , p 16 and p 18 , ( 2 ) downmodulation of the protein expression of cyclin D 1 , cdk 4 and cdk 6 , but not of cyclin E and cdk 2 , ( 3 ) inhibition of the kinase activities associated with cyclin E , cyclin D 1 , cdk 2 , cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , E , A , H , Cdk 1 ( cyclin dependent kinase ; Cdc 2 ) , Cdk 4 , and Cdk 6 protein levels were determined by Western blot analysis at different pathologic stages of liver tissues exhibiting HCC . ^^^ Enzymatic activities of cyclin D 1 , E , A , Cdk 4 , Cdk 6 , Cdc 2 , Cdk 7 , and Wee 1 kinase were measured by in gel kinase assay . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Importantly , CDK 6 can not substitute for CDK 4 in this role , which demonstrates that the 2 cyclin D dependent kinases are functionally different . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The tumour suppressor gene p16 / INK4a encodes a specific inhibitor of the cyclin D dependent kinases CDK 4 and CDK 6 . p16 / INK4a prevents the association of CDK 4 with cyclin D 1 , and subsequently inhibits phosphorylation of retinoblastoma tumour suppressor protein ( pRb ) , thus preventing exit from the G 1 phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Levels of cdk 2 , cdk 4 , and cdk 6 decreased 40 70 % , while levels of cyclin A and B were unaffected by induction of CD 1 antisense . ^^^ Induction of a CD 1 antisense gene in a human colon cancer cell line resulted in rapid , concomitant changes in CD 1 mRNA and protein , cyclin E , cdk 2 , cdk 4 , and cdk 6 , as well as the ratio of ppRb to pRb . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
This effect was associated with a decrease in cyclin dependent kinase ( Cdk ) 2 and , to a lesser extent , Cdk 6 , but not Cdk 4 activity , without changes in Cdk 2 , 4 , and 6 and cyclin D and E protein levels . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We also review our recent structural studies on intracellular signalling complexes , focusing on phosducin transducin GPry , CK 2 protein kinase and its complexes , and the cyclin D dependent kinase , Cdk 6 , bound to the cell cycle inhibitor p19INK4d . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In T cells and fibroblasts Tax enhances the activity of the cyclin dependent kinases ( CDK ) CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We found that the expression of cyclin A and p 21 ( WAF 1 ) molecules was primarily modulated by TGFbeta 1 treatment while the expression of other regulatory components , like cyclins D , cyclin E , cdk 2 , cdk 4 , and cdk 6 or p 15 ( INK4B ) , p 16 ( INK4A ) , and p 27 ( KIP 1 ) was not significantly affected . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
A vitamin D 3 analog induces a G 1 phase arrest in CaCo 2 cells by inhibiting cdk 2 and cdk 6 : roles of cyclin E , p21Waf1 , and p27Kip1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Up regulation of cyclin dependent kinases ( Cdk 4 and Cdk 6 ) and cyclin D 3 was initiated in TCR stimulated T cells entering G1A phase and expression of these markers steadily increased as T cells progressed from G1A into G1B phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
While p15INK4B and its binding to both cdk 4 and cdk 6 increased with increasing passage , some cyclin D 1 bound cdk 4 and cdk 6 persisted in senescent cells , whose inhibition could not be attributed to p15INK4B . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
However , when complexed to cdk 6 , they have several activities that distinguish them from D type cyclin cdk 6 complexes , including resistance to cyclin dependent kinase inhibitors and an enhanced substrate range . ^^^ Using mammalian in vitro replication systems , we show that viral cyclin cdk 6 complexes can directly trigger the initiation of DNA synthesis in isolated late G ( 1 ) phase nuclei . ^^^ Viral cyclin cdk 6 complexes share this capacity with cyclin A cdk 2 , demonstrating that in addition to functioning as G ( 1 ) phase cyclin cdk complexes , they function as S phase cyclin cdk complexes . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Moreover , these cells were incapable of clonal expansion due to defective synthesis of cyclin D 3 and cyclin A , and defective activation of cyclin dependent kinase ( cdk ) 4 , cdk 6 , and cdk 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
No changes in the levels of cyclin E or the catalytic partners of these cyclins , CDK 2 , CDK 4 , or CDK 6 , were observed . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
A potent inhibitor of the cyclin D dependent kinases CDK 4 and CDK 6 . ^^^ Progression through the G 1 phase of the cell cycle requires phosphorylation of the retinoblastoma gene product ( pRb ) by the cyclin D dependent kinases CDK 4 and CDK 6 , whose activity can specifically be blocked by the CDK inhibitor p 16 ( INK4A ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We screened a cohort of 206 patients with clinically localized PC treated with radical prostatectomy for overexpression of the INK4A gene , the product of which inactivates the G 1 phase cyclin dependent kinases , Cdk 4 and Cdk 6 . p16INK4A protein expression was evaluated by immunohistochemistry in areas of high grade intraepithelial neoplasia ( HGPIN ) , a precursor to invasive disease , and of cancer in the same specimen . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Apigenin reduced the protein levels of CDK 4 , cyclins D 1 and A , but did not affect cyclin E , CDK 2 and CDK 6 protein expression . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
RT PCR analysis showed that cyclin D 2 , cyclin D 3 , CDK 4 , and CDK 6 were ubiquitously expressed in normal B cell development and in the BLIN ALL cell lines . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The immunoblot analysis revealed that resveratrol treatment causes a dose and time dependent ( a ) induction of WAF1 / p21 ; ( b ) decrease in the protein expressions of cyclin D 1 , cyclin D 2 , and cyclin E ; and ( c ) decrease in the protein expressions of cdk 2 , cdk 4 , and cdk 6 . ^^^ Taken together , our study suggests that resveratrol treatment of the cells causes an induction of WAF1 / p21 that inhibits cyclin D1 / D2 cdk 6 , cyclin D1 / D2 cdk 4 , and cyclin E cdk 2 complexes , thereby imposing an artificial checkpoint at the G ( 1 ) > S transition of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Statistical analysis using configural frequency analysis and regression analysis revealed that cyclin D 2 and CDK 4 expression were strongly correlated ( r ( 2 ) = 0 . 682 ; P = 0 . 000052 ) , whereas expression of CDK 6 did not correlate with either of them ( r ( 2 ) = 0 . 382 ; P = 0 . 00085 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The kinase activation was found to result from Tax induced expression of genes for cell cycle regulatory molecules including cyclin D 2 , cyclin E , E2F1 , CDK 2 , CDK 4 and CDK 6 , and Tax induced reduction of CDK inhibitors p 19 ( INK4d ) and p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
This was accompanied by a down regulation of cyclin dependent kinases ( cdk ) 4 and cdk 6 as well as cyclin D 1 , while cdk 2 and cyclin E protein levels remained unchanged during mevastatin treatment . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Induction of G 1 cell cycle arrest was also observed in PC 3 cells treated with I3C , which may be due to the observed effects of I3C in the up regulation of p 21 ( WAF 1 ) and p 27 ( Kip 1 ) CDK inhibitors , followed by their association with cyclin D 1 and E and down regulation of CDK 6 protein kinase levels and activity . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The protein levels of cdk 2 , cdk 6 and proliferating cell nuclear antigen were unaffected . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
On laminin , endothelial cells fail to translate Cyclin D 1 mRNA and activate CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The main effect of the ectopic Cdk 6 expression was to sequester TGF beta induced p 15 ( Ink4b ) and to maintain more p 27 ( Kip 1 ) in cyclin D complexes preventing the complete shift of p 27 ( Kip 1 ) to Cdk 2 invoked by TGF beta . ^^^ This led to the presence of an active cyclinD Cdk 6 p27 ( Kip 1 ) complex and partially active cyclin E Cdk 2 complex and resulted in the failure of TGF beta to fully arrest Mv1Lu cell growth . ^^^ The results demonstrate that downregulation of Cdk 6 kinase is required for the enforcement of the G ( 1 ) phase arrest by TGF beta and results in changes in association of the p 15 ( Ink4b ) and p 27 ( Kip 1 ) inhibitors with D and E type cyclin kinase complexes . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Earlier , we have shown that resveratrol treatment results in an induction of the cyclin kinase inhibitor WAF1 / CIP1 / p21 which , by inhibiting cyclin ( E , D 1 , and D 2 ) and cyclin dependent kinases ( cdk 2 , cdk 4 , and cdk 6 ) , results in a G0 / G1 phase arrest followed by apoptosis of A 431 human epidermoid carcinoma cells ( Ahmad et al . , Clin . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
An increase in cyclin dependent kinase 2 ( cdk 2 ) protein expression occurred after 12 h , but no changes in cdk 4 or cdk 6 protein levels were observed . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
A particular role in the regulation of these phenomena is played by proteins involved in early G 1 phase regulation : pRb kinases : cyclin dependent kinases ( cdk ) : cdk 4 and cdk 6 activated by cyclins D , and universal cdk inhibitor p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
P 19 ( INK4d ) is a tumor suppressing protein and belongs to a family of cyclin D dependent kinase inhibitors of CDK 4 and CDK 6 , which play a key role in human cell cycle control . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Recent evidence strongly suggest that the D type cyclins with cdk 4 and cdk 6 form holoenzymes that regulate cell cycle events earlier in G 1 than cyclin E / cdk2 complexes which functions near the G1 / S transition . ^^^ Following activation of splenic derived murine G0T cells , cdk 6 , cyclin D 2 and D 3 specific mRNAs were detected early in G 1 and reached maximal levels prior to or near G1 / S . ^^^ The phosphorylation of retinoblastoma protein from T cells was detected very early in G 1 and was associated mainly with cdk6 / cyclin D 2 complexes which accounted for a minor portion of the total cellular cdk 6 contained in the cytoplasmic fraction of T cells and mostly in the catalytically inactive form . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Evidence for coordinated interaction of cyclin D 3 with p 21 and cdk 6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation . ^^^ Among the various cell cycle molecules examined , coordinate expression and functional association of cyclin D 3 with cdk 4 suggest a role for proliferation and , that of cyclin D 3 with p 21 and cdk 6 is consistent with the development of polyploidy during stromal cell decidualization . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Structural basis for CDK 6 activation by a virus encoded cyclin . ^^^ Cyclin from herpesvirus saimiri ( Vcyclin ) preferentially forms complexes with cyclin dependent kinase 6 ( CDK 6 ) from primate host cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
TGF beta 1 intensified the decreased expression of CDK 2 , CDK 4 , CDK 6 and cyclin D 1 in EB 1089 treated NCI H 929 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In the present study we show that two dimensional ( 2 D ) maps together with immuno detection allow the precise identification of important leukocyte differentiation and tumor markers ( e . g . , CD 3 and CD 5 ) , and important cell cycle regulatory molecules such as cyclin dependent kinases , notably CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
D type cyclins bind cyclin dependent kinases ( Cdk 4 and Cdk 6 ) and are expressed during the transition from G 0 into the S phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Tax stimulates the cell cycle in the G ( 1 ) phase by activating the cyclin dependent kinase ( CDK ) CDK 4 and CDK 6 holoenzyme complexes . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 bound to both cdk 4 and cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Transforming growth factor beta ( TGF beta ) induces G ( 1 ) arrest in susceptible cells by multiple mechanisms that inhibit the G ( 1 ) cyclin dependent kinases ( Cdks ) , including Cdk 2 , Cdk 4 , and Cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The levels of CDK 6 , cyclin D 1 and cyclin A were decreased . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
High expression of cyclin D 2 and time dependent increases in cyclin dependent kinase 6 ( CDK 6 ) and cyclin D 3 were observed in SNU 1103 during serum starvation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
PI3K signalling also participated in cell cycle progression , since PI3K and MAPK coordinately regulated changes in cyclin D 1 and cdk 6 expression . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Ectopic overexpression of Jak 3 in 32Dcl3 cells resulted in an acceleration of the G CSF induced differentiation program that was preceded by G ( 1 ) cell cycle arrest , which was associated with the up regulation of the cyclin dependent kinase inhibitor p 27 ( Kip 1 ) and down regulation of Cdk 2 , Cdk 4 , Cdk 6 , and Cyclin E . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Striking findings were the overexpression of cyclin E , CDK 2 , CDK 6 , STAT 3 , Hdm 2 , Bcl 2 , Bcl 10 ( L ) , survivin , and NF kappaB proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
D type cyclins bind to and activate the cyclin dependent kinases Cdk 4 and Cdk 6 , which in turn phosphorylate their downstream target , the retinoblastoma protein Rb . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Downregulation of the kinase activities is mediated by induction of cyclin dependent kinase ( CDK ) inhibitor p 15 ( Ink4b ) which blocks CDK 4 and CDK 6 kinases and leads to binding of p 27 ( Kip 1 ) to CDK 2 cyclin E complex . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
When we examined the effects of this drug on A 498 cells , arsenic trioxide ( 2 . 5 microM ) decreased the levels of CDK 2 , CDK 6 , cyclin D 1 , cyclin E , and cyclin A proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D cdk 6 complex is targeted by p 21 ( WAF ) in growth arrested lymphoma cells . ^^^ Both cdk 4 and cdk 6 were notably dissociated from cyclin D cofactors , while cyclin E cdk 2 complexes remained coupled in TGFbeta 1 treated cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
This effect is accomplished through VES significantly decreasing expression of the cell cycle regulatory proteins cyclin D 1 , D 3 , and E , cdk 2 and 4 , but not cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We found that ROCK blockade decreased expression of cell cycle proteins , cyclin D 3 , CDK 6 , and p 27 ( KIP 1 ) in the hearts and cardiomyocytes , which are required for initiation of cell cycle and G1 / S phase transition . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
When we examined the effects of this drug on SNU C 1 cells , monensin decreased the levels of CDK 2 , CDK 4 , CDK 6 , cyclin D 1 and cyclin A proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin K resists the actions of the p 16 INK4a and p27Kip1 inhibitors and extends the range of cdk 6 substrates , thereby inducing cell cycle progression toward S phase . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The INK 4 family of cyclin dependent kinase ( CDK ) inhibitors negatively regulates cyclin D dependent CDK 4 and CDK 6 and thereby retains the growth suppressive function of Rb family proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
As shown by immunoblot analysis , EGCG treatment of LNCaP and DU 145 cells resulted in significant dose and time dependent ( 1 ) upregulation of the protein expression of WAF1 / p21 , KIP1 / p27 , INK4a / p16 , and INK4c / p18 , ( 2 ) down modulation of the protein expression of cyclin D 1 , cyclin E , cdk 2 , cdk 4 , and cdk 6 , but not of cyclin D 2 , ( 3 ) increase in the binding of cyclin D 1 toward WAF1 / p21 and KIP1 / p27 , and ( 4 ) decrease in the binding of cyclin E toward cdk 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Overexpression of Cdk 6 cyclin D 3 highly sensitizes cells to physical and chemical transformation . ^^^ Virtually all mammalian cells express two seemingly redundant cyclin D dependent kinases ( Cdk 4 and Cdk 6 ) and three partner cyclins ( D 1 , D 2 and D 3 ) essential for the G ( 1 ) S transition , with predominant expression of Cdk 4 and D 1 in mesenchymal cells and Cdk 6 and D 3 in hematopoietic cells . ^^^ Among the kinase D type cyclin combinations , the Cdk 6 cyclin D 3 complex has a unique ability to evade inhibition by cyclin dependent kinase inhibitors and thereby control the cell ' s proliferative competence under growth suppressive conditions . ^^^ This result suggests that deregulated expression of Cdk 6 and cyclinD 3 may predispose cells to malignant transformation , supporting the recent finding that cyclin D 3 activated by chromosomal rearrangement is the causative gene of non Hodgkin B lymphoma , in which Cdk 6 is the major partner kinase . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The protein levels of cyclins D 1 , E , A , and H , and of cyclin dependent kinase 1 ( Cdk 1 ) , Cdk 2 , Cdk 4 , Cdk 6 , and Cdk 7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot . ^^^ The enhanced cyclin D 1 related kinase activity in HCC was accompanied by the up regulation of Cdk 4 activity , but not Cdk 6 activity . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
When we examined the effects of this drug on ACHN cells , monensin decreased the levels of CDK 2 , CDK 6 , cdc 2 , cyclin A and cyclin B 1 proteins . p 21 and p 27 proteins were increased by monensin . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
When we examined the effects of this drug on ACHN cells , trichostatin decreased the levels of CDK 4 , CDK 6 , cyclin D 1 and cyclin A proteins . p 27 protein was increased by trichostatin . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blot analysis of G ( 1 ) phase regulatory proteins demonstrated that the protein levels of cyclin dependent kinase 2 ( Cdk 2 ) , Cdk 4 , Cyclin E and Cyclin D 3 were decreased after treatment with SCK 6 but not those of Cdk 6 , Cyclin D 1 and D 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Monensin decreased the levels of CDK 2 , CDK 6 , cdc 2 , cyclin A , cyclin B 1 , cyclin D 1 and cyclin E proteins but did not alter CDK 4 protein . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Overexpression of cyclin D 1 , the regulatory subunit of cyclin dependent kinases ( cdk 4 and cdk 6 ) involved in cell cycle control , has often been found in breast cancer and other types of human cancer . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Arsenic increased expression of the P 21 protein and decreased levels of cyclin A , cyclin B 1 and cyclin D 1 , but expression of CDK 2 , CDK 4 , CDK 6 , and cyclin E were not affected . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
While butyrate alone increased p21Waf1 / Cip1 expression and down regulated cdk 6 and cyclin A , and combined exposure with 1 , 25 ( OH ) 2D3 resulted in a synergistic enhancement of butyrate induced changes , expressions did not change from control level after treatment with butyrate and ZK 191732 . ^^^ In conclusion , differentiation and cell cycle arrest of Caco 2 cells induced by butyrate are mediated by up regulation of VDR , followed by a stimulation of the negative cell cycle regulator p21Waf1 / Cip1 and by a down regulation of cdk 6 and cyclin A , both involved in cell cycle progression . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
At least four of these so called cyclin dependent kinases , namely Cdk 4 , Cdk 6 , Cdk 2 and Cdk 1 , have specific roles at particular stages of the cell cycle , including passage through the various cell cycle transitions and the response to specific checkpoints . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
METHODS : Human colon cancer cell lines SW 480 and HCT 116 were transfected with Stat 3 antisense oligonucleotide mediated by liposome , MTT assay was used to measure the proliferation , flow cytometry was applied to analyze the cell cycle , and the expressions of Stat 3 , phosphorylation specific Stat 3 ( tyrosine 705 ) , Cyclin D 1 , Cyclin E , CDK 2 , CDK 4 , CDK 6 , p 21 and p 27 were measured by western blot . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The level of CDK 6 activity was also seen to be reduced following PBOX 21 treatment , also possibly due to a reduction in complex formation with cyclin D ( 3 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The data show that 1 ) . mouse oocytes contain significant amounts of all studied regulators ; 2 ) . their amounts and localization undergo dramatic changes as the oocytes grow , meiotically mature , and transit into embryogenesis ; and 3 ) . some regulators ( CDK 4 , CDK 6 , cyclin D 2 , and p 27 ) appear in unusual , most likely posttranslationally modified , forms . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
To date only one class of substrates have been identified for cyclinD CDK 4 and CDK 6 complexes , those belonging to pRb family of proteins , whereas the list of cyclin E CDK 2 substrates continues to lengthen . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
By real time PCR analysis , PhIP induced rat mammary gland carcinomas showed statistically higher expression of the G ( 1 ) S cyclin D 1 ( 5 fold ) and its kinase partner cyclin dependent kinase ( Cdk ) 4 ( 37 fold ) in comparison with normal mammary gland , whereas cyclin D 2 , cyclin D 3 , and Cdk 6 were not statistically changed . ^^^ By immunohistochemical analysis , cyclin D 1 , Cdk 4 , and phospho Rb nuclear protein expression was 5 . 7 , 3 . 9 , and 2 . 3 fold higher , respectively , in carcinomas than in normal mammary gland , whereas the expression of cyclin D 2 , cyclin D 3 , and Cdk 6 was similar . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
This effect was accompanied by the decreased expression of G ( 1 ) associated proteins including cyclin D 1 , CDK 4 , and Rb phosphorylation at Ser 780 , Ser 795 , and Ser807 / 811 , whereas expression of CDK 6 and beta actin was not affected by LY 294002 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
To study the molecular mechanisms of cell cycle regulation by AESR , we also measured the intracellular levels of cell cycle regulatory proteins such as cyclin D , cyclin dependent kinases ( CDK ) 4 , CDK 6 , cyclin E , CDK 2 , p 53 , p21WAF1 / CIP1 and p16INK4A . ^^^ The levels of cyclin E and CDK 2 were increased in HOMFs after 100 microg / ml of AESR treatment , but the levels of cyclin D , CDK 4 , and CDK 6 were unchanged . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , and later Cdk 2 , in association with their specific cyclin partners , regulate the G 1 to S phase cell cycle transition of mammalian cells by phosphorylation of retinoblastoma ( Rb ) family proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The interruption of cell cycle progression in the presence of thialysine was accompanied by a significant decline in the protein level of cdk 4 , cdk 6 , cdc 2 , cyclin A , cyclin B 1 , and cyclin E . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cdk 6 cyclin D 3 activity in murine ES cells is resistant to inhibition by p 16 ( INK4a ) . ^^^ Cdk 6 is the major catalytic partner for cyclin D 3 in ES cells and exhibits robust pRb kinase activity that is downregulated during the early stages of ES embryoid body differentiation . ^^^ To investigate the basis underlying the insensitivity of ES cells to ectopic p 16 expression , we show that Cdk 6 cyclin D 3 complexes are not subject to inhibition by p 16 , similar to Cdk viral cyclin complexes . ^^^ Our data suggest that Cdk 6 cyclin D 3 activity in other cell types , including tumors , may also be refractory to p 16 mediated growth inhibition and raises the possibility of additional specificity within the INK 4 family . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Specifically , 18 genes were present in both signatures , including genes that code for cell cycle regulatory proteins ( cyclin A 2 , cyclin D 3 , cyclin H , CDK 6 , p18INK4c , p21Cip1 , PAK 1 ) and centrosome associated proteins ( pericentrin , alpha 2 tubulin , NUMA 1 , TUBGCP 2 , PRKAR2A ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
AGN 194204 dependent suppression of MIA PaCa 2 cell proliferation is associated with reduced cyclin E and cyclin dependent kinase 6 ( cdk 6 ) level , but cyclin D 1 , cdk 2 and cdk 4 content is not altered . ^^^ The RXR selective antagonist , AGN 195393 , reverses the AGN 194204 dependent growth inhibition and the decline in cyclin E and cdk 6 levels . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression of key cell cycle regulatory proteins was affected in the G ( 1 ) phase : the expression of cyclin D 3 , CDK 2 , p 27 , and E2F 4 was up regulated , and the expression of cyclin D 2 , CDK 6 , p 21 , and p 103 was down regulated during serum starvation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In rasREF cells treated with DE for 72 h in suspension culture ( a ) , the levels of cyclin D 1 , cyclin A , p 27 ( Kip 1 ) , and hyperphosphorylated Rb were decreased , but the levels of cdk 4 , cdk 6 , cdk 2 , p 16 ( INK4a ) , and p 21 ( Cip 1 ) were not affected . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
It has long been assumed that the action of cyclin D 1 , as an activator of cdk 4 and cdk 6 and leading to progression through the G 1 phase of the cell cycle , underlies its pathological activity . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 1 , cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 was measured quantitatively by real time polymerase chain reaction . ^^^ These results indicate that cyclin D 1 may be involved in the regeneration of hepatocytes rather than hepatocarcinogenesis , while Cdk 4 but not Cdk 6 may play an important role in the development of HCC . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 expression estimated by a real time reverse transcription polymerase chain reaction ( RT PCR ) method was also increased markedly at an early stage of cirrhosis development but decreased substantially thereafter . mRNA levels of catalytic subunits of cyclin D 1 , cyclin dependent kinase 4 ( Cdk 4 ) and Cdk 6 , did not show significant changes during the development of liver cirrhosis . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
While the amounts of the cellular cyclin dependent kinase ( Cdk ) inhibitors p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , and p 16 ( INK4a ) did not change in infected cells , MHV infection in asynchronous cultures induced a clear reduction in the amounts of Cdk 4 and G ( 1 ) cyclins ( cyclins D 1 , D 2 , D 3 , and E ) in both DBT and 17Cl 1 cells and a reduction in Cdk 6 levels in 17Cl 1 cells . ^^^ MHV infection in quiescent 17Cl 1 cells prevented normal increases in Cdk 4 , Cdk 6 , cyclin D 1 , and cyclin D 3 levels after serum stimulation . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Osteoclast differentiation by RANKL requires NF kappaB mediated downregulation of cyclin dependent kinase 6 ( Cdk 6 ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Furthermore , Western blot analysis showed decreased expression levels of cyclin D 1 , cyclin E , cyclin A , Cdk 2 , Cdk 4 , and Cdk 6 proteins . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Moreover , we show that 5 cyclin and cyclin dependent kinase 6 ( CDK 6 ) form an active kinase without p 27 ( KIP 1 ) and that CDK 6 is the in vivo catalytic subunit of 5 cyclin in PEL cells . ^^^ These findings suggest that KSHV may promote oncogenesis in PEL by expressing 5 cyclin , which both overrides negative cell cycle controls present in the PEL precursor cells and induces a strong proliferative signal via CDK 6 kinase activity . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Activation through the TCR results in rapid transport of cytoplasmic cyclin dependent kinase 6 ( cdk 6 ) to nuclei , where it associates with cyclin D and p 57 ( Kip 2 ) in active enzyme complexes . ^^^ Using purified recombinant proteins , it was shown in vitro that addition of p 57 ( Kip 2 ) protein to a mixture of cyclin D 2 and cdk 6 enhanced the association of the latter two proteins and resulted in phosphorylation of p 57 ( Kip 2 ) . ^^^ Induction of p 57 ( Kip 2 ) resulted in increased association of cdk 6 with cyclin D 3 , without receptor mediated T cell stimulation . ^^^ The overall amounts of cdk 6 and cyclin D 3 , and also of cdk 4 and cyclin E , remained unchanged . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 is found to play a crucial role not only in progression through the G 1 phase as a regulatory subunit of cyclin dependent kinase 4 ( CDK 4 ) and CDK 6 , but also in many other aspects such as cell cycle , cell differentiation , transcriptional regulation and apoptosis . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Western blotting was used for caspase 3 and PARP , caspase 7 , caspase 9 , cytochrome c , Bcl 2 , Bax , Mcl 1 , cyclinA , cyclin B 1 , cyclin D 1 , cyclin E , CDK 2 , CDK 4 , CDK 6 , P 21 , P 27 , GADD 45 , GADD 153 . ^^^ The expression of cyclin A and cyclin B 1 was markedly decreased and cyclin D 1 levels were slightly lowered in AsPC 1 cells , while cyclin E was not affected and the levels of CDK 2 , CDK 4 , and CDK 6 were unchanged in MiaPaCa 2 and AsPC 1 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression of cyclin D 2 mRNA did not decline until 12 h after hCG , although both cyclin dependent kinase ( Cdk ) 4 and Cdk 6 mRNA increased at 6 h . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , D 2 and D 3 , and Cdk 4 , Cdk 6 and Rb protein , and Cyclin D 1 mRNA expression were measured in primary patient derived neuroblastoma cell lines . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The results showed that NaB and / or ATRA blocked cells mainly in the G0 / G1 phase of the cell cycle ; ATRA inhibited the mRNA expression of CDK 6 , CDK 4 , cyclin D 3 and cyclin D 1 ; NaB inhibited the mRNA expression of CDK 2 , cyclin D 2 and cyclin D 1 ; ATRA and NaB inhibited the mRNA expression of CDK 6 , CDK 4 , CDK 2 , cyclin D 1 , cyclin D 2 and cyclin D 3 ; ATRA and / or NaB both stimulated p 21 expression at the mRNA levels . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The levels of expression of G1 / S phase related proteins , such as cyclin D 1 , cyclin dependent kinase ( cdk ) 4 , cdk 6 , and proliferating cell nuclear antigen , were reduced and a cdk inhibitor , p 21 ( Cip 1 ) , was induced in rPCT 1 CM treated TR iBRB 2 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Although the latter was complexed with PCNA , Cdk 2 , Cdk 4 , Cdk 6 , cyclin D 3 , and cyclin E , truncated p 21 was bound only to Cdk 4 and cyclin D 3 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
However , recent experiments in which the genes encoding all three D type cyclins , the two E type cyclins , cyclin D dependent Cdk 4 and Cdk 6 , or cyclin E dependent Cdk 2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Biochip analysis showed that SWCNTs can induce up regulation expression of cell cycle associated genes such as p 16 , bax , p 57 , hrk , cdc 42 and cdc 37 , down regulation expression of cell cycle genes such as cdk 2 , cdk 4 , cdk 6 and cyclin D 3 , and down regulation expression of signal transduction associated genes such as mad 2 , jak 1 , ttk , pcdha 9 and erk . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
First , tetrandrine inhibits purified cyclin dependent kinase 2 ( CDK 2 ) / cyclin E and CDK 4 without affecting significantly CDK2 / cyclin A , CDK1 / cyclin B , and CDK 6 . ^^^ Second , tetrandrine induces the proteasome dependent degradation of CDK 4 , CDK 6 , cyclin D 1 , and E2F1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Early onset of G 1 cell cycle arrest along with upregulation of the cyclin dependent kinase inhibitor p27Kip1 and downregulation of Cdk 2 , Cdk 4 , Cdk 6 , and Cyclin E has also been observed in Jak 3 overexpressing 32Dcl3 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In contrast , Cdk 6 is activated by the Kaposi ' s sarcoma associated herpesvirus ( KSHV ) cyclin in the absence and presence of CAK phosphorylation . ^^^ KSHV cyclin complexes was investigated here by analyzing mutants of the KSHV cyclin and Cdk 6 in vitro as well as in U2OS cells . ^^^ Mutation of residues in the region 180 200 of the KSHV cyclin decreases the binding affinity to Cdk 6 in U2OS cells but increases the activity of Cdk6 . ^^^ Expression of high levels of p 16 ( INK4a ) in cells leads to the formation of a heterotrimeric complex composed of Cdk 6 , KSHV cyclin , and p 16 ( INK4a ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Among all D type cyclin / cdk4 and cdk 6 complexes , cyclin D3 / cdk4 is most active in sequestering the inhibitory activity of p 27 ( kip 1 ) in vitro in a cyclinE / cdk2 kinase assay . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Here , c Myb was identified as part of a protein complex from human T cells containing the cyclin dependent kinase ( CDK ) CDK 6 . ^^^ Assays using model reporter constructs as well as endogenous target genes showed that the activity of c Myb was inhibited by cyclin D 1 plus CDK 4 or CDK 6 but stimulated by expression of the CDK inhibitors p 16 Ink4a , p 21 Cip1 , or p 27 Kip1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We describe here the crystal structure of human CDK 6 in complex with a viral cyclin and a flavonol inhibitor , fisetin . ^^^ Fisetin binds to the active form of CDK 6 , forming hydrogen bonds with the side chains of residues in the binding pocket that undergo large conformational changes during CDK activation by cyclin binding . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In cell culture studies , TGF beta 1 significantly inhibited proliferation of MBEC via downregulation of cyclin D 1 , cdk 4 , and cdk 6 , while TGF beta 1 did not influence the proliferation of ICC cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Consistent with G ( 1 ) arrest in DU 145 cells , decursin strongly increased protein levels of Cip1 / p21 but showed a moderate increase in Kip1 / p27 with a decrease in cyclin dependent kinases ( CDK ) ; CDK 2 , CDK 4 , CDK 6 , and cyclin D 1 , and inhibited CDK 2 , CDK 4 , CDK 6 , cyclin D 1 , and cyclin E kinase activity , and increased binding of CDK inhibitor ( CDKI ) with CDK . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cell cycle progression without cyclin D CDK 4 and cyclin D CDK 6 complexes . ^^^ D type cyclins ( cyclin D 1 , D 2 and D 3 ) and their associated cyclin dependent kinases CDK 4 and CDK 6 were thought to represent important , perhaps essential components of the core cell cycle apparatus . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase 6 ( CDK 6 ) binds to and is activated by cyclin D 1 and thereby enhances the transition of cells through the G 1 phase of the cell cycle . ^^^ This effect of CDK 6 does not require its kinase activity and is inhibited by cyclin D 1 and p16INK4a . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The expression status of the three cyclin D genes ( CCND 1 , CCND 2 and CCND 3 ) , the two cyclin D dependent kinase genes ( CDK 4 and CDK 6 ) and the p 16 ( INK4a ) gene was studied in a series of 47 Wilms ' tumors , 16 normal mature kidneys and two fetal kidneys . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
CDKs are activated by association with cyclin and are inhibited by complexation with small molecules . 10 ray crystal structures are available for three of the thirteen known CDK family members : CDK 2 , CDK 5 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In many tissues mitogens influence development by stimulating D type cyclins ( D 1 , D 2 , or D 3 ) and activating cyclin dependent kinases ( CDK 4 or CDK 6 ) , which results in progression through the G ( 1 ) phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
METHODS : We used immunoprecipitation with K cyclin antibodies to examine the association of K cyclin with cdk 2 , cdk 6 , p21Cip1 , and p27Kip1 proteins in BC 3 cells . ^^^ RESULTS : Viral K cyclin interacted with cyclin dependent kinases cdk 2 , cdk 4 , and cdk 6 and with the cyclin / cdk inhibitory proteins p21Cip1 and p27Kip1 in BC 3 cell lysates . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The Cyclin dependent kinase ( CDK ) Activating Kinase ( CAK ) is responsible for the activating phosphorylation of CDK 1 , CDK 2 , CDK 4 and CDK 6 and regulation of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Both , p 16 , cyclin D 1 , cdk 4 and cdk 6 were immuno colocalized with Ezrin , Rac , Vinculin , alphav integrin , and FAK proteins in the ruffles and lamellipodia of migratory cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
It was demonstrated in CD34+ cell extracts that there was high catalytic activity of G ( 1 ) cyclin dependent kinases 4 and 6 ( CDK 4 and CDK 6 ) but low activity of CDK 2 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
The cell cycle arrest involves downregulation of cyclin D 1 , cyclin E , cyclin dependent kinase ( CDK ) 2 , CDK 4 , and CDK 6 and upregulation of p 15 , p 21 , and p 27 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
D cyclins ( D 1 , D 2 and D 3 ) and their catalytic subunits ( cyclin dependent kinases cdk 4 and cdk 6 ) have a facilitating , but nonessential , role in cell cycle entry . ^^^ Fbxo 7 specifically regulated D cyclin / cdk6 complexes : Fbxo 7 knockdown decreased cdk 6 association with cyclin and its overexpression increased D cyclin / cdk6 activity and E2F activity . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
We show that , in contrast to the Kaposi ' s sarcoma associated herpesvirus ( KSHV ) 5 cyclin , the gammaHV 68 5 cyclin preferentially interacts with cdk 2 and cdc 2 but does not interact with either cdk 4 or cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 3 up regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK 4 and CDK 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 , but not its enzyme Cdk 6 , was also depleted after the CHL treatments ; the depletions were associated with elevations of G0 / G1 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Here we demonstrate that 5 cyclin together with its kinase partner CDK 6 phosphorylates the associated p 27 ( KIP 1 ) in PEL cells , which represent a biologically relevant model system for KSHV pathobiology . ^^^ During latent viral replication p 27 ( KIP 1 ) was phosphorylated by 5 cyclin CDK 6 predominantly on Ser 10 , which enhances its cytoplasmic localization . ^^^ Interestingly , upon reactivation of KSHV lytic cycle , 5 cyclin CDK 6 phosphorylated p 27 ( KIP 1 ) on Thr 187 , which resulted in down regulation of p 27 ( KIP 1 ) protein levels . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Immunoblot analysis revealed that PFE treatment of PC 3 cells resulted in ( 1 ) induction of Bax and Bak ( proapoptotic ) ; ( 2 ) down regulation of Bcl 10 ( L ) and Bcl 2 ( antiapoptotic ) ; ( 3 ) induction of WAF1 / p21 and KIP1 / p27 ; ( 4 ) a decrease in cyclins D 1 , D 2 , and E ; and ( 5 ) a decrease in cyclin dependent kinase ( cdk ) 2 , cdk 4 , and cdk 6 expression . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Molecular studies showed that G 1 arrest was associated with a decrease in cyclin D 1 , cyclin D 3 , cyclin E , cyclin dependent kinase ( CDK ) 4 , CDK 6 and CDK 2 protein levels , and CDK 2 and CDK 4 kinase activity , together with an increase in CDK inhibitors ( CDKIs ) Kip1 / p27 and Cip1 / p21 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cells exposed to 17 AAG and LY 294002 displayed a significant reduction in cell cycle regulatory proteins , such as retinoblastoma ( Rb ) , cyclin dependent kinase ( CDK ) 4 , CDK 6 , cyclin D 1 , and cyclin D 3 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Using tissue microarrays ( TMAs ) , we have analysed the immuno expression of Ki 67 , Bcl 2 , Bax , cyclin D 1 , cyclin D 3 , CDK 1 , CDK 2 , CDK 6 , p 16 , p 21 , and p 27 in a series of 205 carcinomas of the large bowel , breast , lung and prostate ( 80 , 73 , 37 and 15 cases , respectively ) . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
After analyzing the cellular proteins involving in regulation of cell cycle progression , we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D 3 level of mRNA transcription and expression , and phosphorylation of retinoblastoma ( Rb ) protein at ser 795 and ser809 / 811 , not with the expression of cyclin D 1 , D 2 , cdk 4 and cdk 6 in HEK 293 cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 or D 3 expression does not vary in the clinical course , but that alone is insufficient to promote cell cycle progression unless cyclin dependent kinase 4 ( cdk 4 ) is also elevated , in the absence of cdk 6 , to phosphorylate the retinoblastoma protein ( Rb ) . ^^^ By contrast , cyclin D 2 and cdk 6 are coordinately increased , thereby overriding the inhibition by cdk inhibitors p 18 ( INK4c ) and p 27 ( Kip 1 ) and phosphorylating Rb in conjunction with the existing cdk 4 . ^^^ Thus , cyclin D 1 pairs exclusively with cdk 4 and cdk 6 pairs only with cyclin D 2 , although cyclin D 2 can also pair with cdk 4 in multiple myeloma cells . ^^^ In addition , cyclin D 1 or cyclin D 3 expressing multiple myeloma cells are uniformly distributed in the bone marrow , whereas cdk 6 specific phosphorylation of Rb occurs in discrete foci of bone marrow multiple myeloma cells before proliferation early in the clinical course and is then heightened with proliferation and disease progression . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Intriguingly , down regulation of TSC proteins was also observed by the expression of a mutant cyclin D 1 that is unable to bind to CDK4 / 6 , or by the coexpression of cyclin D 1 with either an INK 4 inhibitor or with catalytically inactive CDK 6 , indicating that cyclin D may regulate TSC 1 TSC2 independently of CDK4 / 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
DIM also induced a G 1 arrest in DU 145 cells by flow cytometry and downstream concurrent inhibition of cell cycle parameters such as cyclin D 1 , cdk 4 , and cdk 6 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D 1 is a multifunctional protein that activates CDK 4 and CDK 6 , titrates Cip / Kip CDK inhibitors to increase CDK 2 activity , and modulates the function of certain transcription factors . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Concomitantly , compared to EV control cells , PKC delta upregulation decreased cyclin D 1 and cyclin E proteins co immunoprecipitating with cdk 6 and cdk 2 , respectively . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
This was supported by down regulation of cyclin D 1 , cdk 4 , and cdk 6 in rap1GAP transfected SCC cells . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
In Myc deficient cells , despite its inability to overcome this proliferation block , 5 Src was able to regulate the expression of certain Myc transcriptional targets and induce the expression of active cyclin D / Cdk4 and Cdk 6 complexes ; it also induced the phosphorylation of Rb , albeit at reduced levels . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
K cyclin encoded by Kaposi ' s sarcoma associated herpesvirus confers resistance to the cyclin dependent kinase ( cdk ) inhibitors p16Ink4A , p21Cip1 , and p27Kip1 on the associated cdk 6 . ^^^ Thus , expression of the viral cyclin enables cells to subvert the cell cycle inhibitory function of p21Cip1 by promoting cdk 6 dependent phosphorylation of this antiproliferative protein . . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
RESULTS : cDNA array analysis showed that cyclin B 1 , MCM 5 , MCM 7 , RAD 9 , ubiquitin C , CDK 6 , SKP 2 , and APAF 1 were up regulated in malignant thyroid neoplasms . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Oral intake of apigenin resulted in dose dependent ( a ) increase in the protein expression of WAF1 / p21 , KIP1 / p27 , INK4a / p16 , and INK4c / p18 ; ( b ) down modulation of the protein expression of cyclins D 1 , D 2 , and E ; and cyclin dependent kinases ( cdk ) , cdk 2 , cdk 4 , and cdk 6 ; ( c ) decrease in retinoblastoma phosphorylation at serine 780 ; ( d ) increase in the binding of cyclin D 1 toward WAF1 / p21 and KIP1 / p27 ; and ( e ) decrease in the binding of cyclin E toward cdk 2 in both types of tumors . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin D dependent Cdk 4 and Cdk 6 were expressed in most of a panel of six human rhabdomyosarcoma derived cell lines . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G ( 1 ) S transition and proteins that regulate apoptosis including Rb , E2F1 , cyclin D 1 , CDK 4 , CDK 6 , p 27 ( KIP 1 ) , p 21 ( WAF1 / CIP1 ) , p 53 , Mdm 2 , Bcl 2 , and Bax . ^^^ The positive phenotypes identified were as follows : Rb , 39 . 1 % ; E2F1 , 69 . 6 % ; cyclin D 1 , 30 . 4 % ; CDK 4 , 100 % ; CDK 6 , 30 . 4 % ; 39 . 1 % ; p 27 ( KIP 1 ) , 47 . 8 % ; p 21 ( WAF1 / CIP1 ) , 39 . 1 % ; p 53 , 43 . 5 % ; Mdm 2 , 17 . 4 % ; Bcl 2 , 91 . 3 % ; and Bax , 100 % . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Cyclin dependent kinase ( cdk ) 4 and cdk 6 have historically been understood to be D cyclin kinases that phosphorylate pRb in the nucleus to regulate G 1 phase of the cell cycle . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Some important cell cycle regulators were reduced in rho 0 cells : cyclin D 3 , cdk 6 , p18INK4C , p27KIP1 , and p21CIP1 / WAF1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Within cyclin D 3 complexes , T loop phosphorylation of CDK 4 , but not of CDK 6 , was directly regulated , identifying it as a determining target for cell cycle control by extracellular factors . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Finally , immunoprecipitation studies showed that CDK 6 is a major binding partner for cyclin D 3 , whereas CDK 4 preferentially associated with cyclin D 1 . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
Membrane depolarization induced by 50 mM KCl for 5 min significantly increased SH SY5Y cell numbers and thymidine incorporation at 24 h after depolarization , and increased the phosphorylation and expression of retinoblastoma protein ( RB ) , the activity of Cdk 2 ( without changing the activities of Cdk 4 and Cdk 6 ) , and the expressions of cyclin A and cyclin E . ^^^
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
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Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q00534 and P12004	Pubmed	SVM Score :0.0
NA