Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.85635525
Conversely , p45Skp2 is associated with p27Kip1 both in the nucleus and in the cytoplasm , accumulating within the nuclei after exposure to LMB and co localizing with the exportin CRM 1 , suggesting a possible involvement of p45Skp2 in CRM 1 dependent nuclear export of p27Kip1 . 0.85635525^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.6978625
A specific association was observed between Skp 2 and a p 27 carboxy terminal peptide containing phosphorylated Thr 187 , but not between Skp 2 and the non phosphorylated peptide . 0.6978625^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.80792379
All three binding sites of Cks 1 are required for p 27 ubiquitin ligation and for the association of Skp 2 with Cdk bound , Thr 187 phosphorylated p 27 . 0.80792379^^^ All proteins of this family have Cdk binding and anion binding sites , but only mammalian Cks 1 binds to Skp 2 and promotes the association of Skp 2 with p 27 phosphorylated on Thr 187 . 0.59118048^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.71614968
VD / EB1089 significantly restricted the association of p 27 with Skp 2 as well as with cyclin dependent kinase 2 ( CDK 2 ) . 0.71614968^^^ Vitamin D and its analog EB 1089 induce p 27 accumulation and diminish association of p 27 with Skp 2 independent of PTEN in pituitary corticotroph cells . 0.66468941^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :1.0559709
Using this assay , we have determined the dissociation constant of the Skp 2 Cks1 complex ( K ( d ) 140 + / 14 nM ) and have shown that Skp 2 binds phosphorylated p 27 peptide with high affinity only in the presence of Cks 1 ( K ( d ) 37 + / 2 nM ) . 1.0559709^^^ Here we report the development of a homogeneous time resolved fluorescence assay that allows the quantification of the molecular interactions between human recombinant Skp 2 , Cks 1 and a p 27 derived peptide phosphorylated on Thr ( 187 ) . 0.53036659^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.70885854
We examined the relationship between p 27 and its specific ligase Skp 2 in normal and malignant prostate tissues . 0.70885854^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.56416312
Despite up regulation of the proteasome dependent degradation of p 27 protein , neither threonine 187 phosphorylated p 27 nor skp 2 ( the ubiquitin ligase for p 27 ) were increased . 0.56416312^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.69214464
Ubiquitination of p27Kip1 requires physical interaction with cyclin E and probable phosphate recognition by SKP 2 . p27Kip1 is an essential cell cycle inhibitor of Cyclin dependent kinases . 0.69214464^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.52563194
The crystal structure of the Skp 1 Skp2 Cks 1 complex bound to a p 27 ( Kip 1 ) phosphopeptide shows that Cks 1 binds to the leucine rich repeat ( LRR ) domain and C terminal tail of Skp 2 , whereas p 27 ( Kip 1 ) binds to both Cks 1 and Skp 2 . 0.52563194^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Cks 1 associates with the F box protein Skp 2 and is essential for recognition of the p27Kip1 substrate for ubiquitination in vivo and in vitro . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Metabolic stabilization of p 27 in senescent fibroblasts correlates with reduced expression of the F box protein Skp 2 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The F box protein Skp 2 ( Fbl 1 ) is a positive regulator of G 1 S transition and promotes ubiquitin mediated proteolysis of the cyclin dependent kinase inhibitor p 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Expression of the F box protein SKP 2 is inversely correlated with p 27 in many cancers . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The F box protein Skp 2 positively regulates the G 1 S transition by promoting degradation of the cyclin dependent kinase inhibitor p 27 ( kip 1 ) ( p 27 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The cyclin dependent kinase ( CDK ) inhibitor p27Kip1 plays a key role in growth and development of the mammary epithelium and in breast cancer . p27Kip1 levels are regulated through ubiquitin / proteasome mediated proteolysis , promoted by CDK 2 and the F box protein Skp 2 at the G1 / S transition , and independent of Skp 2 in mid G 1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Using cell viability assay , we established the optimal in vitro inhibitory dose of celecoxib and showed that inhibition of COX 2 markedly induces the expression of p27kip1 , p 21 , waf 1 , and the F box protein skp 2 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
BACKGROUND & OBJECTIVE : The F box protein Skp 2 is required for the ubiquitin mediated proteolysis of the cyclin depended kinase inhibitor p 27 ( kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We speculate that the F box protein Skp 2 , in addition to utilizing Cul 1 Skp1 , utilizes Cul4A DDB 1 to induce proteolysis of p27Kip1 . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Expression of p45SKP2 in quiescent fibroblasts promotes p27Kip1 degradation , allows the generation of cyclin A dependent kinase activity and induces S phase . ^^^ Coexpression of a degradation resistant p27Kip1 mutant suppresses p45SKP2 induced cyclin A kinase activation and S phase entry . ^^^ We propose that p45SKP2 is important in the progression from quiescence to S phase and that the ability of p45SKP2 to promote p27Kip1 degradation is a key aspect of its S phase inducing function . ^^^ In transformed cells , p45SKP2 may contribute to deregulated initiation of DNA replication by interfering with p27Kip1 function . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Increase of p27KIP1 correlates with down regulation of p45SKP2 , a component of the ubiquitin protein ligase SCF ( SKP 2 ) controlling the half life of regulatory proteins during the cell cycle . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Prognostic significance of p27Kip1 , p45Skp2 and Ki 67 expression profiles in Merkel cell carcinoma , extracutaneous small cell carcinoma , and cutaneous squamous cell carcinoma . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Upregulation of p27Kip1 protein in 1 , 25 dihydroxyvitamin D 3 treated cancer cells is mediated via enhancement of gene transcription and reduction of protein degradation . 1 , 25 dihydroxyvitamin D 3 inhibits the expression of p45Skp2 , the F box protein which is implicated in p27Kip1 degradation , to reduce turnover of p27Kip1 protein . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Zearalenone treatment of MCF 7 cells elicited expression of F box protein S phase kinase associated protein 2 ( p 45 ( SKP 2 ) ) , a substrate specific component of the ubiquitin ligase complex that targets p 27 ( KIP 1 ) for degradation in the proteasome . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The F box protein S phase kinase associated protein 2 ( Skp 2 ) positively regulates the G 1 S transition by controlling the stability of several G 1 regulators , such as the cell cycle inhibitor p27kip1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Human CDK subunit 1 ( Cks 1 ) and S phase kinase associated protein 2 ( Skp 2 ) are components of the SCF ( Skp 2 ) complex , which acts as a ubiquitin ligase for p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
S Phase kinase associated protein 2 ( SKP 2 ) , an F box protein constituting the substrate recognition subunit of the SCF ( SKP 2 ) ubiquitin ligase complex , targets cell cycle regulators , such as the cyclin dependent kinase inhibitor p 27 ( KIP 1 ) , for ubiquitin mediated degradation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Because p 27 ( Kip 1 ) is regulated through either degradation , mediated by the S phase kinase associated protein 2 ( Skp 2 ) , or sequestration , via D 3 cyclin , the expression of these proteins was also investigated . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
In this pathway Skp 2 ( S phase kinase associated protein 2 ) plays a critical role in degrading cyclin dependent kinase inhibitor p 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Decreased levels of p 27 ( KIP 1 ) are caused , at least in part , by an acceleration of degradation with Skp 2 ( S phase kinase associated protein 2 ) and Jab 1 ( Jun activation domain binding protein 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PURPOSE : The F box protein S phase kinase associated protein 2 ( Skp 2 ) positively regulates the G ( 1 ) S phase transition by controlling the stability of several G ( 1 ) regulators , such as p27Kip1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
OBJECTIVES : To analyze p 27 and S phase kinase associated protein 2 ( Skp 2 ) expression in upper urinary tract transitional cell carcinoma ( TCC ) with respect to biologic significance . p 27 ( p27 / kip1 ) is involved in cell cycle control , and loss of p 27 protein expression may result in tumor development and / or progression . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PURPOSE : The F box protein S phase kinase associated protein 2 ( Skp 2 ) is one of the positive regulators of the cell cycle that promote ubiquitin mediated proteolysis of the cyclin dependent kinase inhibitor p 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Stabilization of p27kip1 by LXR ligands was mediated by supressing the transcriptional activation of the S phase kinase associated protein 2 ( Skp 2 ) , an F box protein that targets p27Kip1 for degradation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
S phase kinase associated protein 2 ( SKP 2 ) , a member of the F box family of ubiquitin protein ligase complexes , controls the stability of cell cycle related proteins including p27Kip1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
In the present study , we observed increased S phase kinase associated protein 2 mRNA expression in IL 16 null mice , but basal expression and activation dependent regulation of p 27 ( Kip 1 ) were no different from wild type mice . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 ( S phase kinase associated protein 2 ) controls progression from G to S phase by promoting the proteolysis of the cyclin dependent kinase inhibitor p27KIP1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
S phase kinase associated protein 2 ( Skp 2 ) is a member of an F box family of substrate recognition subunits of SCF ubiquitin protein ligase complexes that has been implicated in the ubiquitin mediated degradation of several key regulators of mammalian G 1 progression , including the cyclin dependent kinase inhibitor p27Kip1 , a dosage dependent tumor suppressor protein . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Because p27Kip1 mutation is extremely rare in human tumors , expression of p27Kip1 protein is thought to be controlled by post transcriptional mechanism involved in inactivator , S phase kinase associated protein 2 ( Skp 2 ) and Jun activation domain binding protein 1 ( Jab 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
In addition , p 27 ( Kip 1 ) protein is thought to be degraded by Skp 2 ( S phase kinase associated protein 2 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
BACKGROUND : S phase kinase associated protein 2 ( Skp 2 ) ubiquitin ligase p 45 ( SKP 2 ) is important in the degradation of p27kip1 ( a cyclin dependent kinase inhibitor ) and progression through the G 1 S cell cycle checkpoint . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
BACKGROUND & OBJECTIVE : S phase kinase associated protein 2 ( Skp 2 ) is a positive regulator of G 1 S transition and promotes ubiquitin mediated proteolysis of cyclin dependent kinase inhibitor P 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The conventional pathway to breakdown of p27Kip1 is mediated by S phase kinase associated protein 2 ; however , our evidence suggests that PKCtheta acts via a distinct , unknown pathway inducing G 1 arrest after IL 7 withdrawal from T cells . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We studied the role of S phase kinase associated protein 2 ( Skp 2 ) , an F box protein of SCFSkp 2 ubiquitin ligase responsible for polyubiquitylation of and subsequent proteolysis of p27Kip1 , a key step leading to cell cycle progression . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Increased p 27 ( Kip 1 ) protein levels following the transfection of IKKalpha specific siRNAs are a result of the downregulation of the F box protein S phase kinase associated protein 2 ( skp 2 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Kip 1 meets SKP 2 : new links in cell cycle control . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Activation of CDK 2 and binding to SKP 2 or p 27 ( KIP 1 ) were not affected by the phosphorylation of Ser 154 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Modification of cullin 1 by ubiquitin like protein Nedd 8 enhances the activity of SCF ( skp 2 ) toward p 27 ( kip 1 ) . ^^^ The ubiquitin ligase ( E 3 ) toward p 27 ( kip 1 ) is thought to be SCF ( skp 2 ) . ^^^ When the effect of the Nedd 8 modification on the SCF ( skp 2 ) activity toward p 27 ( kip 1 ) was investigated , the activity was markedly decreased by using the Nedd 8 unmodified mutant cullin 1 ( K696R ) , indicating that the modification may play an important role on the SCF ( skp 2 ) activity toward p 27 ( kip 1 ) . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Degradation of p 27 is initiated by phosphorylation of p 27 at Thr 187 , which marks the protein for ubiquitination by SCF ( Skp 2 ) and subsequent proteolysis by the 26S proteasome . ^^^ Moreover , we show that reconstitution of the p 27 ubiquitination activity of recombinant SCF ( Skp 2 ) also requires Nedd 8 conjugation pathway components . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Targeted disruption of Skp 2 results in accumulation of cyclin E and p 27 ( Kip 1 ) , polyploidy and centrosome overduplication . ^^^ Skp 2 ( / ) cells also exhibit increased accumulation of both cyclin E and p 27 ( Kip 1 ) . ^^^ These results suggest that specific degradation of cyclin E and p 27 ( Kip 1 ) is mediated by the SCF ( Skp 2 ) ubiquitin ligase complex , and that Skp 2 may control chromosome replication and centrosome duplication by determining the abundance of cell cycle regulators . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The cell cycle inhibitor p 27 ( kip 1 ) is a known target of the SCF ( SKP 2 ) complex , and Myc induced Cul 1 expression matched well with the kinetics of declining p 27 ( kip 1 ) protein . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The presence of the CDK inhibitor p 27 ( Kip 1 ) also prevented the SKP 2 dependent degradation of cyclin E . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PTEN regulates the ubiquitin dependent degradation of the CDK inhibitor p 27 ( KIP 1 ) through the ubiquitin E 3 ligase SCF ( SKP 2 ) . ^^^ Our findings suggest that SKP 2 functions as a critical component in the PTEN / PI 3 kinase pathway for the regulation of p 27 ( KIP 1 ) and cell proliferation . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Inverse relation between levels of p 27 ( Kip 1 ) and of its ubiquitin ligase subunit Skp 2 in colorectal carcinomas . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Cyclin E and p27Kip1 each bind to and undergo polyubiquitination by the same ubiquitin ligase , known as SCF ( Skp 2 ) . ^^^ The degradation of cyclin E and p27Kip1 is greatly impaired in Skp 2 deficient mice , resulting in intracellular accumulation of these proteins . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 , an F box protein necessary for DNA replication , is required for the ubiquitinylation and subsequent degradation of p 27 ( Kip 1 ) . ^^^ In the present study , we examined the expression of Skp 2 and its correlation with the expression of p 27 ( Kip 1 ) protein or p 27 ( Kip 1 ) degradation in OSCC . ^^^ Interestingly , OSCC tissues with Skp 2 expression had high p 27 ( Kip 1 ) degradation activity . ^^^ These findings indicate that ( a ) Skp 2 may play an important role for the development of OSCC , ( b ) Skp 2 can be a novel target for OSCC treatment as well as a strong prognostic marker , and ( c ) the reduction in p 27 ( Kip 1 ) protein may be brought about by enhancement of its degradation mediated by increased levels of Skp 2 protein . . ^^^ We also found an inverse correlation between the expression of Skp 2 and p 27 by immunohistochemical analysis . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Targeting of the cyclin dependent kinase inhibitor p 27 ( Kip 1 ) for proteolysis has been thought to be mediated by Skp 2 , the F box protein component of an SCF ubiquitin ligase complex . ^^^ Degradation of p 27 ( Kip 1 ) at the G ( 0 ) G ( 1 ) transition mediated by a Skp 2 independent ubiquitination pathway . ^^^ Degradation of p 27 ( Kip 1 ) at the G ( 0 ) G ( 1 ) transition of the cell cycle has now been shown to proceed normally in Skp 2 ( / ) lymphocytes , whereas p 27 ( Kip 1 ) proteolysis during S G ( 2 ) phases is impaired in these Skp 2 deficient cells . ^^^ The first cell cycle of stimulated Skp 2 ( / ) lymphocytes appeared normal , but the second cycle was markedly inhibited , presumably as a result of p 27 ( Kip 1 ) accumulation during S G ( 2 ) phases of the first cell cycle . ^^^ Polyubiquitination of p 27 ( Kip 1 ) in the nucleus is dependent on Skp 2 and phosphorylation of p 27 ( Kip 1 ) on threonine 187 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Involvement of p 27 ( KIP 1 ) degradation by Skp 2 in the regulation of proliferation in response to wounding of corneal epithelium . ^^^ PURPOSE : To examine the expression of the p 27 ( KIP 1 ) in the normal and epithelial scraped cornea and whether degradation of p 27 ( KIP 1 ) by Skp 2 is involved in the regulation of cell proliferation in response to wounding of the corneal epithelium . ^^^ METHODS : C57Bl6 , p 27 ( KIP 1 / ) , Skp 2 ( / ) , and Skp 2 ( / ) / p27 ( KIP 1 / ) double knockout mice were examined . ^^^ Twenty four hours after epithelial scraping in the Skp 2 ( / ) mice , the corneal epithelium was thinner than in wild type mice and had many p 27 ( KIP 1 ) positive cells and few BrdU positive cells . ^^^ In contrast , 24 hours after epithelial scraping in the Skp 2 ( / ) / p27 ( KIP 1 ) ( / ) double knockout mice , the corneal epithelium was as thick as in wild type mice and had many BrdU positive cells . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
As p 27 phosphorylation and association with Skp 2 is a key step in its degradation , we examined the effects of VD / EB1089 on this reaction . ^^^ Despite increased total p 27 , the pThr content of p 27 remained unaffected , an effect confirmed by diminished association with Skp 2 as well as in situ phosphorylation . ^^^ These findings point to a novel mechanism of action for VD / EB1089 inhibition of thyroid carcinoma cell growth by p 27 hypophosphorylation , diminished association with Skp 2 , and consequent accumulation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The abundance of p 27 ( Kip 1 ) , an inhibitor of cell proliferation , is determined by Skp 2 dependent proteolysis , the deregulation of which is associated with cancer progression . ^^^ Lack of Skp 2 results in p 27 ( Kip 1 ) accumulation as well as enlargement and polyploidy of hepatocytes . ^^^ Skp 2 ( / ) mice exhibited restoration of liver mass without cell proliferation ; rather , hepatocytes increased in size , an effect that was accompanied by increased polyploidy and p 27 ( Kip 1 ) accumulation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The nuclear export and subsequent degradation of p 27 ( Kip 1 ) at the G ( 0 ) G ( 1 ) transition were observed in cells lacking Skp 2 , the F box protein component of an SCF ubiquitin ligase complex , indicating that these early events are independent of Skp 2 mediated proteolysis . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
To determine whether there were alterations of p 27 and the target proteins implicated in the ubiquitin degradation of p 27 and other cyclin dependent kinase inhibitors , we examined expression of SKP 2 , Grb 2 , and Jab 1 in the pituitaries of null mice . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
SKP 2 positively regulates progression of cell cycle by targeting several regulators , such as the cell cycle inhibitor p 27 ( KIP 1 ) , for ubiquitin mediated degradation . ^^^ There was an inverse correlation between the expression of SKP 2 and p 27 ( KIP 1 ) proteins . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Both cell lines spontaneously expressed Skp 2 and cyclin D 1 proteins at high levels but no p 27 ( Kip 1 ) protein . ^^^ In the presence of LY 294002 , cell cycle arrest in G0 / G1 was observed , p 27 ( Kip 1 ) protein expression was up regulated whereas the expression of both Skp 2 and cyclin D 1 dramatically diminished . ^^^ Most of the biological effects of PI 3 K activation in these cell lines may be mediated by the opposite modulation of p 27 ( Kip 1 ) and Skp 2 protein expression . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Expression of Skp 2 , a p 27 ( Kip 1 ) ubiquitin ligase , in malignant lymphoma : correlation with p 27 ( Kip 1 ) and proliferation index . ^^^ Skp 2 , a component of the Skp 1 Cul1 F box protein ( SCF ) ubiquitin ligase complex , has been implicated in p 27 ( Kip 1 ) degradation . ^^^ Increased Skp 2 levels are seen in some solid tumors and are associated with reduced p 27 ( Kip 1 ) . ^^^ We studied the expression of Skp 2 in low grade and aggressive B cell lymphomas ( n = 86 ) and compared them with p 27 ( Kip 1 ) and the proliferation index ( PI ) . ^^^ Skp 2 expression in small lymphocytic lymphomas ( SLLs ) and follicular lymphomas ( FCLs ) was low ( mean percentage of positive tumor cells , less than 20 % ) and was inversely correlated ( r = 0 . 67 ; P < . 0001 ) with p 27 ( Kip 1 ) and positively correlated with the PI ( r = 0 . 82 ; P < . 005 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
As for this mechanism , GATA 2 was found to inhibit ubiquitin / proteasome dependent degradation of p 21 ( WAF 1 ) and p 27 ( Kip 1 ) and to induce their accumulation by repressing the expression of Skp 2 and Cul 1 , both of which are components of the ubiquitin ligase for p 21 ( WAF 1 ) and p 27 ( Kip 1 ) . ^^^ Overexpression of c myc restored the expression of Skp 2 and Cul 1 mRNA , reduced the amounts of p 21 ( WAF 1 ) and p 27 ( Kip 1 ) proteins , and canceled GATA 2 induced growth suppression , suggesting that down regulation of c myc expression may be primarily responsible for GATA 2 induced growth suppression . ^^^ GATA 2 / ER suppressed cytokine dependent growth of MNCs and Sca 1 ( + ) Lin ( ) cells by about 70 % , which was also accompanied by the reduced expression of c myc , Skp 2 , and Cul 1 mRNA and the accumulation of p 21 ( WAF 1 ) and p 27 ( Kip 1 ) proteins . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Along with the reduction in p 27 ( Kip 1 ) protein , PAX 3 FKHR expressing cells exhibited elevated expression of F box Skp 2 protein , a substrate specific component of SCF ( Skp 1 Cullin F box protein ) ligase involved in the cell cycle dependent control of p 27 ( Kip 1 ) ubiquitination and 26 S proteasome dependent degradation . ^^^ PAX 3 FKHR transformation increases 26 S proteasome dependent degradation of p27Kip1 , a potential role for elevated Skp 2 expression . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Over expression of p 45 ( SKP 2 ) in Kaposi ' s sarcoma correlates with higher tumor stage and extracutaneous involvement but is not directly related to p 27 ( KIP 1 ) down regulation . ^^^ F Box protein p 45 ( SKP 2 ) is the substrate specific receptor of ubiquitin protein ligase SCF / p45 ( SKP 2 ) and is involved in the degradation of p 27 ( Kip 1 ) through the ubiquitin / proteasome pathway . ^^^ The aim of this study was to determine whether p 45 ( SKP 2 ) expression is altered in aggressive lesions of Kaposi ' s sarcoma and its relation to p 27 ( KIP 1 ) down regulation . ^^^ No statistically significant differences were found in regard to patients ' sex and human immunodeficiency virus status and regression analysis failed to show a correlation among p 45 ( SKP 2 ) , p 27 ( KIP 1 ) and Ki 67 immunostaining scores . ^^^ These findings suggest that p 45 ( SKP 2 ) is involved in Kaposi ' s sarcoma progression , not only by promoting the degradation of p 27 ( KIP 1 ) but also through other mechanisms still unknown . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Immunoblotting and in vitro ubiquitination assays indicated that the expression of Cul 1 and Skp 2 and ubiquitination activity toward p 27 ( Kip 1 ) were not regulated by NSAIDs . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Finally , our results show that PI 3 kinase mediated proliferation of erythroid progenitors in response to Epo occurs mainly through modulation of the E 3 ligase SCF ( SKP 2 ) , which , in turn , down regulates p 27 ( Kip 1 ) cyclin dependent kinase ( CDK ) inhibitor via proteasome degradation . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Inhibition of F Box protein p 45 ( SKP 2 ) expression and stabilization of cyclin dependent kinase inhibitor p 27 ( KIP 1 ) in vitamin D analog treated cancer cells . ^^^ This suggests that 1 , 25 ( OH ) ( 2 ) D ( 3 ) treatment may be stabilizing p 27 ( KIP 1 ) protein , which is sensitive to modification by the SCF ( SKP 2 ) protein ubiquitin ligase and proteosomal degradation . ^^^ EB 1089 treatment repressed expression of mRNAs encoding the F box protein p 45 ( SKP 2 ) , a marker of poor head and neck cancer prognosis , and the cyclin kinase subunit CKS 1 , which is essential for targeting p 45 ( SKP 2 ) to p 27 ( KIP 1 ) . ^^^ This coincided with a reduction of total p 45 ( SKP 2 ) protein , and p 45 ( SKP 2 ) associated with p 27 ( KIP 1 ) . ^^^ A similar reduction in p 45 ( SKP 2 ) expression and stabilization of p 27 ( KIP 1 ) protein was observed in 1 , 25 ( OH ) ( 2 ) D ( 3 ) sensitive UF 1 promyelocytic leukemia cells , which also respond by transiently increasing p 27 ( kip 1 ) gene transcription . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
METHODS : Clinicopathologic features and immunohistochemical expression of Skp 2 , p 27 , and Ki 67 proteins were studied in 182 cases of soft tissue sarcomas ( American Joint Committee on Cancer stages 2 and 3 ) . ^^^ High Skp 2 expression ( > or = 10 % of the cells ) was identified in 68 tumors ( 37 % ) , and was correlated with high grade histology ( P = . 002 ) and Ki 67 proliferative index ( r = 0 . 44 ; P < . 0001 ) , but not with p 27 expression ( r = 0 . 02 ; P = . 80 ) . ^^^ The lack of an inverse correlation between Skp 2 and p 27 suggests that additional molecular events associated with either Skp 2 expression or p 27 proteolysis may be operating in these tumors . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Simultaneous accumulations in both p 27 ( Kip 1 ) and cyclin E are known to be characteristic phenotypes in cells derived from mice lacking Skp 2 , an F box protein component of the SCF ubiquitin ligase complex . ^^^ Thus , the aim of the present study was to assess whether Skp 2 might be involved in the down regulation of p 27 ( Kip 1 ) in troglitazone treated human hepatoma cells . ^^^ A striking decrease in Skp 2 expression and a reciprocal increase in p 27 ( Kip 1 ) expression were found in troglitazone treated hepatoma cells but not in those cells treated with other PPARgamma ligands such as pioglitazone and ciglitazone . ^^^ In conclusion , troglitazone attenuated Skp 2 expression , thereby promoting p 27 ( Kip 1 ) accumulation in human hepatoma cells . ^^^ Troglitazone induces p27Kip1 associated cell cycle arrest through down regulating Skp 2 in human hepatoma cells . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PGI overexpressing cells also exhibited elevated expression of Skp 2 involved in p27Kip1 ubiquitination and elevation in the levels of retinoblastoma protein hyperphosphorylation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
A negatively charged amino acid in Skp 2 is required for Skp 2 Cks1 interaction and ubiquitination of p27Kip1 . ^^^ Ubiquitination of p 27 requires the SCFSkp 2 ubiquitin ligase and Skp 2 F box binding protein Cks 1 . ^^^ The mechanisms by which Skp 2 recognizes Cks 1 to ubiquitylate p 27 remain obscure . ^^^ Here we show that Asp 331 in the carboxyl terminus of Skp 2 is required for its association with Cks 1 and ubiquitination of p 27 . ^^^ Although Asp 331 mutation negates the ability of the Skp 1 Cullin F box protein ( SCF ) complex to ubiquitylate p 27 , such a mutation has no effect on Skp 2 self ubiquitination . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Furthermore , induction of p27Kip1 and reduction of cyclin E and Skp 2 were detected by Western blotting . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We found a significant accumulation of p 27 ( KIP 1 ) in response to BMP 2 , whereas the expression level of Skp 2 , which is required for ubiquitin dependent p 27 ( KIP 1 ) degradation , was decreased during this differentiation process . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We used as a model system the SCF ( Skp 2 ) complex that targets p 27 ( Kip 1 ) for ubiquitination and subsequent degradation ; this process requires an adapter protein , Cks 1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 is the F box protein component of an SCF type ubiquitin ligase that interacts specifically with p 27 ( Kip 1 ) and thereby promotes its ubiquitylation and degradation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Mutation of the threonine residue ( Thr 310 ) of human p57Kip2 that is conserved between the COOH terminal QT domains of p57Kip2 and p27Kip1 prevented the effect of Skp 2 on the stability of p57Kip2 , suggesting that phosphorylation at this site is required for SCFSkp 2 mediated ubiquitylation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Because Cdk 2 mediated phosphorylation of p 27 at Thr 187 targets p 27 for Skp 2 mediated degradation , we examined the phosphorylation status of p 27 in 1 , 25 ( OH ) 2D3 treated cells . 1 , 25 ( OH ) 2D3 decreased levels of Thr 187 phosphorylated p 27 , consistent with inhibition of Thr 187 phosphorylation dependent p 27 degradation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
To further examine the mechanism of the troglitazone induced p 27 ( Kip 1 ) protein accumulation , 2 major systems for regulation of p 27 ( Kip 1 ) protein , proteasome activity and Skp 2 , an F box protein that targets p 27 ( Kip 1 ) for degradation , were evaluated . ^^^ Growth arrest by troglitazone is mediated by p27Kip1 accumulation , which results from dual inhibition of proteasome activity and Skp 2 expression in human hepatocellular carcinoma cells . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Although over expression of Cks 1 protein as well as it of Skp 2 might be associated with tumour progression via p27Kip1 protein degradation , it is unknown how the cellular level of Cks 1 is regulated . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We also found that the decrease in p 27 ( Kip 1 ) induced by IGF 1 was accompanied by an increase in expression of Skp 2 , which is a ubiquitin ligase for p 27 ( Kip 1 ) , and by increased Skp 2 association with p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
METHOD AND RESULTS : C57B16 mouse , p 27 ( KIP 1 ) / mice , Skp 2 / mice and Skp 2 / / p27 ( KIP 1 ) / double knockout mice were examined by immunocytochemistry using anti p 27 ( KIP 1 ) antibody , and cells in the `` S ' ' phase of DNA synthesis were analyzed by immunocytochemistry using anti BrdU antibody . ^^^ There was no obvious difference in the thickness and anti BrdU staining in the corneal epithelium of p 27 ( KIP 1 ) / mice from that of controls . 24 hr after the epithelial scraping in the Skp 2 / mice , the corneal epithelium was thinner than in wild type mice and had many p 27 ( KIP 1 ) positive cells and few BrdU positive cells . ^^^ In contrast , 24 hr after the epithelial scraping in the Skp 2 / / p 27 ( KIP 1 ) / double knockout mice , the corneal epithelium was as thick as in wild type mice and had many BrdU positive cells . ^^^ CONCLUSIONS : These results suggest that degradation of p 27 ( KIP 1 ) by Skp 2 is involved in the regulation of proliferation in response to wounding of the corneal epithelium . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The deficiency of Cks 1 in TGF beta treated cells likely contributes to the stabilization of p27Kip1 and destabilization of Skp 2 , because in the absence of Cks 1 , SCFSkp 2 can not ubiquitinate p27Kip1 ; instead , self ubiquitination of Skp 2 occurs . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Nuclear pro IL 16 regulation of T cell proliferation : p 27 ( KIP 1 ) dependent G0 / G1 arrest mediated by inhibition of Skp 2 transcription . ^^^ Pro IL 16 decreases p 27 ( KIP 1 ) degradation by reducing transcription and subsequent expression of Skp 2 , a key component of the SCF ( Skp 2 ) ubiquitin E 3 ligase complex . ^^^ Taken together , these findings identify pro IL 16 as a novel regulator of Skp 2 expression and p 27 ( KIP 1 ) levels and implicate a role for pro IL 16 in T cell proliferation . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Induction of ERbeta reduces growth of exponentially proliferating cells with a concomitant decrease in components of the cell cycle associated with proliferation , namely cyclin E , Cdc25A ( a key regulator of Cdk 2 ) , p 45 ( Skp 2 ) ( a key regulator of p 27 ( Kip 1 ) proteolysis ) , and an increase in the Cdk inhibitor p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
CBP null tumors show reduced levels of p27Kip1 and increased levels of cyclin E and Skp 2 , two oncoproteins that can promote p27Kip1 proteolysis . ^^^ Reduction of p27Kip1 by introduction of a p27Kip1 null allele into CBP knockout mice accelerates lymphomagenesis and seems to obviate the requirement for Skp 2 and cyclin E upregulation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The authors showed that S phase kinase protein 2 ( Skp 2 ) , the specific ubiquitin ligase subunit that targets p 27 ( Kip 1 ) for degradation , was overexpressed and was inversely related to p 27 ( Kip 1 ) levels in patients with colorectal carcinoma . ^^^ METHODS : Quick frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate polyacrylamide gels , transferred to nitrocellulose , and probed with highly specific monoclonal antibodies directed against Cks 1 , Skp 2 , and p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Kip 1 ) stabilization and G ( 1 ) arrest by 1 , 25 dihydroxyvitamin D ( 3 ) in ovarian cancer cells mediated through down regulation of cyclin E / cyclin dependent kinase 2 and Skp 1 Cullin F box protein / Skp2 ubiquitin ligase . p 27 ( Kip 1 ) ( p 27 ) is a tumor suppressor whose stability is controlled by proteasome mediated degradation , a process directed in part by cyclin dependent kinase 2 ( CDK 2 ) mediated phosphorylation of p 27 at Thr ( 187 ) and its subsequent interaction with the Skp 1 Cullin F box protein / Skp2 ( Skp 2 ) ubiquitin ligase . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Cells accumulating p 27 ( kip 1 ) and arrested in mid G ( 1 ) phase when spreading were inhibited by restricted extracellular matrix adhesion , whereas constitutively active RhoA increased expression of the F box protein Skp 2 required for ubiquitination dependent degradation of p 27 ( kip 1 ) and restored G ( 1 ) progression in these cells . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Unlike differentiating J2E cells , Mlf 1 expressing cells did not downregulate Cul 1 and Skp 2 , components of the ubiquitin E 3 ligase complex SCF ( Skp 2 ) involved in the proteasomal degradation of p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We previously reported that the prostacyclin mimetic , cicaprost , selectively inhibits cyclin E cyclin dependent kinase 2 ( Cdk 2 ) , and now we show that it acts by regulating the expression of Skp 2 , the F box protein that targets p 27 ( Kip 1 ) for ubiquitin mediated proteolysis . ^^^ Moreover , we show that cicaprost blocks the induction of Skp 2 mRNA and that ectopic expression of a Skp 2 cDNA overrides the effect of cicaprost on p 27 ( Kip 1 ) levels and S phase entry . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Ubiquitin dependent proteolysis of p 27 ( kip 1 ) is growth and cell cycle regulated in two ways : first , skp 2 , a component of the E 3 ubiquitin ligase , is growth regulated , and second , a kinase must phosphorylate the threonine 187 position on p 27 so that it can be recognized by skp 2 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Overexpression of wild type Skp 2 in SMCs decreased p 27 ( Kip 1 ) levels , whereas dominant negative F box deleted mutant ( DeltaF Skp 2 ) Skp 2 increased p 27 ( Kip 1 ) levels . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
SKP 2 , an F box protein constituting the substrate recognition subunit of the SCF ( SKP 2 ) ubiquitin ligase complex , is implicated in ubiquitin mediated degradation of the cyclin dependent kinase inhibitor p 27 ( KIP 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
ARF expression also led to decreased levels of Cul 1 and Skp 2 , two proteins involved in p 27 degradation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Evidence for impaired Skp 2 dependent degradation of p 27 in terminal differentiation . ^^^ Biochemical analysis demonstrated that Skp 2 dependent p 27 ubiquitylation was remarkably suppressed in cardiomyocytes , whereas Skp 2 , a component of Skp 1 Cullin F box protein ubiquitin ligase , was more actively ubiquitylated compared with proliferating rat fibroblasts . ^^^ Specific degradation of p 27 by co expressing Skp 2 or p 27 small interfering RNA caused an increase of CDK 2 activity and overrode the limited cell cycle . ^^^ These data altogether indicate that the impaired Skp 2 dependent p 27 degradation is causally related to the loss of proliferation in cardiomyocytes . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Increase of Skp 2 , which is involved in the degradation of cell cycle regulators including p27Kip1 , p 21 and c myc , is one of the important mechanisms for dysregulation of cell cycles in various cancers . ^^^ HIV lentivirus mediated RNAi for Skp 2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp 2 through the increase of p27Kip1 and p 21 , but no significant effect on the growth of cells without high Skp 2 expression . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Rb interacts with the N terminus of Skp 2 , interferes with Skp 2 p27 interaction , and inhibits ubiquitination of p 27 . ^^^ Disruption of p 27 function or expression of the Skp 2 N terminus prevents Rb from causing G 1 arrest . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Late in the cell cycle , p 27 degradation requires phosphorylation of Thr 187 by cyclin dependent kinase 2 , leading to recognition by the SCF ubiquitin ligase containing the Skp 2 F box protein . ^^^ Suppression of p 27 is also essential for cell proliferation early in the cell cycle , but this occurs independently of Skp 2 , whose expression is suppressed during G 1 phase . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Biological significance of p 27 and Skp 2 expression in renal cell carcinoma . ^^^ Association with Skp 2 targets p 27 for degradation . ^^^ Using a tissue microarray technique , 171 primary renal cell carcinomas ( RCCs ) and 58 RCC metastases were immunostained for p 27 and Skp 2 . p 27 Immunoreactivity was noted in 83 of 129 ( 64 % ) clear cell , 6 of 22 ( 27 % ) chromophobe and 15 of 20 ( 75 % ) papillary tumours as well as 44 of 58 ( 76 % ) metastases . ^^^ In multivariate analysis , patients with low p 27 expression and Skp 2 immunoreactivity in clear cell cancers had a less favourable outcome . ^^^ In conclusion , p 27 and Skp 2 proved to be additional biomarkers in renal cancer pathology with both prognostic and diagnostic impact . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 dependent degradation of p27kip1 is essential for cell cycle progression . ^^^ Here we show that the loss of a single skp 2 substrate , namely , the cyclin kinase inhibitor p27kip1 , reverts the phenotype of skp 2 knockout hepatocytes to normal . ^^^ By comparing the kinetics of p 27 turnover and cell cycle progression in skp 2 knockout and p27T187A knock in mice , we define a short period in G 1 in which p 27 is able to block the cell cycle after the exit from quiescence . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Although the nuclear ubiquitin ligase ( E 3 ) SCF ( Skp 2 ) is implicated in p 27 ( Kip 1 ) degradation , proteolysis of p 27 ( Kip 1 ) at the G 0 G1 transition proceeds normally in Skp 2 ( / ) cells . ^^^ These data suggest the existence of a Skp 2 independent pathway for the degradation of p 27 ( Kip 1 ) at G 1 phase . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Repression of p 27 ( Kip 1 ) was accompanied by a dramatic reduction in KIP 1 mRNA and was observed in primary mouse embryo fibroblasts derived from mice either lacking SKP 2 or expressing a T187A mutated form of p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 overexpression is a p27Kip1 independent predictor of poor prognosis in patients with biliary tract cancers . ^^^ However , levels of Skp 2 and p27Kip1 proteins were not correlated inversely . ^^^ Heightened expression of Skp 2 and reduced expression of p27Kip1 were both associated with a shorter disease free and / or overall survival in univariate analyses . ^^^ In multivariate regression analyses , Skp 2 and p27Kip1 were independent predictive factors . ^^^ Those results suggest that ( a ) overexpression of Skp 2 through an amplification mechanism may contribute to the progression of BTC , ( b ) not only each molecule , but also the combination of Skp 2 and p27Kip1 , might be a useful predictor of the prognosis of BTC , and ( c ) molecular targets of Skp 2 other than p27Kip1 may also be important factors in the pathogenesis of this disease . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Downregulation of both Skp 2 and p 27 increased apoptosis synergistically . ^^^ Cyclin E levels and cyclin E CDK 2 kinase activity increased dramatically when both Skp 2 and p 27 were downregulated . ^^^ Moreover , stable expression of Bcl 2 also abrogated apoptosis induced by downregulation of Skp 2 and p 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : The expression of Skp 2 , Cks 1 , and p27Kip1 was examined by immunohistochemistry using highly specific antibodies on formalin fixed , paraffin embedded tissue sections from 80 patients with colorectal carcinoma . ^^^ RESULTS : Overexpression of Skp 2 and Cks 1 strongly correlated with loss of p27Kip1 and loss of tumor differentiation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
This degradation depends on the ubiquitinylation of p 27 ( Kip 1 ) by Skp 2 containing SFC complexes : silencing the expression of Skp 2 with a small interfering RNA results in the accumulation of p 27 ( Kip 1 ) . ^^^ Finally , expression of a p 27 ( Kip 1 ) mutant unable of being recognized by Skp 2 results in inhibition of proliferation of BCR ABL cells , indicating that the degradation of p 27 ( Kip 1 ) contributes to the pathogenesis of CML . ^^^ BCR ABL induces the expression of Skp 2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Notch 1 modulates timing of G 1 S progression by inducing SKP 2 transcription and p 27 Kip1 degradation . ^^^ Up regulation of SKP 2 by Notch signaling enhances proteasome mediated degradation of the CKIs , p 27 Kip1 and p 21 Cip1 , and causes premature entry into S phase . ^^^ Silencing of SKP 2 by RNA interference in G 1 stabilizes p 27 Kip1 and p 21 Cip1 and abolishes Notch effect on G 1 S progression . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Effective inhibition of cell growth and invasion of melanoma by combined suppression of BRAF ( V599E ) and Skp 2 with lentiviral RNAi . p27Kip1 that regulates the G1 / S transition of cell cycle and inhibits Rho A signaling is frequently lost in several cancers leading to the deregulation of cell growth and cell motility . ^^^ Skp 2 , a subunit of an SCF ubiquitin protein ligase complex responsible for the ubiquitination of p27Kip1 , is upregulated frequently in several cancers , leading to the decrease of p27Kip1 . ^^^ We applied human immunodeficiency virus ( HIV ) lentivirus mediated RNA interference ( RNAi ) to melanoma cells with the BRAF mutation ( V599E ) and overexpressed Skp 2 and found that the simultaneous suppression of these activated oncogenes resulted in the effective inhibition of in vitro cell growth and invasive ability of melanoma cells accompanied by the additional increase of p27Kip1 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PURPOSE : Skp 2 interacts with the degradation of cyclin dependent kinase inhibitor p 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The present study was undertaken to examine the role of Cks 1 expression in breast cancer and its relation to p27Kip1 and Skp 2 expression and to tumor aggressiveness . ^^^ METHODS : The expressions of Cks 1 , Skp 2 , and p27Kip1 were examined immunohistochemically on formalin fixed , paraffin wax embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines . ^^^ RESULTS : The expression of Cks 1 was strongly associated with Skp 2 expression ( r = 0 . 477 ; P = 0 . 001 ) and inversely with p27Kip1 ( r = 0 . 726 ; P < 0 . 0001 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
In particular , over expression of CKS1B , which maps to an amplicon at 1q21 in myeloma and regulates SCF ( Skp 2 ) mediated ubquitination and proteolysis of the cyclin dependent kinase inhibitor p27Kip1 was significantly over expressed in patients with poor survival . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
We have previously shown that ectopic expression of Pro IL 16 in Pro IL 16 negative human Jurkat cells represses transcription of the F box protein , Skp 2 , resulting in accumulation of the cyclin dependent kinase inhibitor , p 27 ( Kip 1 ) , and G0 / G1 cell cycle arrest . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PI3K / Akt signaling regulates p 27 ( kip 1 ) expression via Skp 2 in PC 3 and DU 145 prostate cancer cells , but is not a major factor in p 27 ( kip 1 ) regulation in LNCaP and PC 346 cells . ^^^ As shown in LNCaP cells , p 27 ( kip 1 ) expression inversely correlated with Skp 2 expression , but Skp 2 was not regulated by Akt . ^^^ Blocking PI3K / Akt signaling in PC 3 cells resulted in decreased Skp 2 protein expression and increased p 27 ( kip 1 ) . ^^^ Downregulation of PTEN in DU 145 cells also showed PTEN / Akt dependent regulation of Skp 2 and p 27 ( kip 1 ) . ^^^ CONCLUSIONS : In PC 3 and DU 145 cells , Skp 2 is the main determinant in the PI3K / Akt dependent regulation of p 27 ( kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
PURPOSE : Two SCF ( Skp 2 ) ubiquitin ligase related proteins , Skp 2 and cyclin dependent kinase subunit 1 ( Cks 1 ) , are involved in posttranscriptional degradation of p 27 ( Kip 1 ) tumor suppressor . ^^^ EXPERIMENTAL DESIGN : Clinicopathologic features and tissue microarray based immunohistochemical expression of p 27 ( Kip 1 ) , Skp 2 , Cks 1 , cyclin E , cyclin A , Ki 67 , and minichromosome maintenance protein 2 ( Mcm 2 ) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes . ^^^ Skp 2 mRNA expression and the relationship between Skp 2 and p 27 ( Kip 1 ) proteins were examined in six cases by semiquantitative reverse transcription PCR and Western blotting , respectively . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Recently , it has been reported that S phase kinase interacting protein 2 ( Skp 2 ) , the specific ubiquitin ligase subunit that targets p27Kip1 for degradation , was overexpressed and was inversely related to p27Kip1 levels in malignant melanoma with poor prognosis . ^^^ OBJECTIVE : We investigated whether small interfering RNA ( siRNA ) mediated gene silencing of Skp 2 can be employed in order to inhibit p27Kip1 down regulation and suppress melanoma cell growth as a consequence in vitro and in vivo . ^^^ RESULTS : Skp 2 protein was decreased and the p27Kip1 protein was accumulated in Skp 2 siRNA transfected melanoma cells . ^^^ CONCLUSION : Our results suggest that siRNA mediated gene silencing of Skp 2 can be a potent tool of cancer gene therapy for suppression of p27Kip1 degradation in malignant melanoma . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Furthermore , we found that FoxM 1 regulates the expression of Skp 2 protein , which is known to promote degradation of the cell cycle regulator p 27 ( Kip 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
These results indicate that APC activation by Tax causes inactivation of SCF ( Skp 2 ) and stabilization of p 21 ( CIP1 / WAF1 ) and p 27 ( KIP 1 ) . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
In response to DNA damage , the level of p 27 gradually increased in normal cells independently of the ataxia telangiectasia mutated / p53 pathway , whereas Skp 2 , an F box protein component of an SCF ubiquitin ligase complex that targets p 27 , was reduced . ^^^ Additionally , p 27 levels in MYCN overexpressing cells were restored by treatment with Skp 2 small interfering RNA , indicating that down regulation of p 27 by MYCN was due to high expression of Skp 2 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Particularly , we did not detect the down regulation of Skp 2 and Cks 1 , two proteins involved in the nuclear ubiquitin dependent p27Kip1 removal . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 is required for endothelial cell proliferation as a consequence of degrading p 27 . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Skp 2 contains a novel cyclin A binding domain that directly protects cyclin A from inhibition by p27Kip1 . ^^^ Skp 2 is well known as the F box protein of the SCF ( Skp 2 ) 10 Roc 1 complex targeting p 27 for ubiquitylation . ^^^ Furthermore , a short peptide derived from the mapped cyclin A binding sequences of Skp 2 can block Skp 2 cyclin A interaction but not p 27 cyclin A interaction , whereas a previously identified RXL peptide can block p 27 cyclin A interaction but not Skp 2 cyclin A interaction . ^^^ Functionally , Skp 2 cyclin A interaction is separable from Skp 2 ability to mediate p 27 ubiquitylation . ^^^ Rather , Skp 2 cyclin A interaction serves to directly protect cyclin A Cdk 2 from inhibition by p 27 through competitive binding . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
The upregulated p27Kip1 level is caused by protein stability increment by the reduction of Skp 2 , a key molecule related with p27Kip1 ubiquitination and degradation , and de novo protein synthesis . ^^^ RVS extract induces G 1 cell cycle arrest via accumulation of p27Kip1 controlled by Skp 2 reduction and apoptosis passing through an intrinsic pathway in human gastric cancer cells but not in normal cells , therefore we suggest that this extract could be a candidate medicine or compound for the development of novel class of anti cancer drugs . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Although combined overexpression of Skp 2 and Cks 1 rescues p 27 degradation in S phase , it can not override p 27 accumulation in G ( 1 ) phase and cell cycle arrest by oncostatin M . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Deregulation of p 27 is commonly observed in many human cancers secondary to enhanced ubiquitin mediated degradation , mediated and rate limited by its specific ubiquitin ligase subunits Skp 2 and Cks 1 . ^^^ Overexpression of Skp 2 and Cks 1 was observed in aggressive CRC and is responsible for down regulation of p 27 levels . ^^^ Both Skp 2 and Cks 1 were found to be independent prognostic markers for survival and provide predictive information additional to that provided by p 27 alone . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Taken together , these results indicated that integrin beta ( 1A ) might upregulate the protein amount of p 27 through repressing Skp 2 dependent proteasome degradation and calpain mediated proteolysis in SMMC 7721 cells . . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
Ubiquitination of p 27 ( kip 1 ) is performed by the SCF ( skp 2 ) ubiquitin ligase comprised of the core components Roc 1 , Cul 1 and Skp 1 and the substrate recognition components Skp 2 and Cks 1 . ^^^ Thus , in primary T lymphocytes CD 28 costimulation can directly regulate cell cycle progression by inducing transcription of the substrate recognition components of SCF ( skp 2 ) ubiquitin ligase that targets p 27 ( kip 1 ) for degradation . . ^^^ CD 28 costimulation mediates transcription of SKP 2 and CKS 1 , the substrate recognition components of SCFSkp 2 ubiquitin ligase that leads p27kip1 to degradation . ^^^
Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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Interacting proteins: Q13309 and P46527	Pubmed	SVM Score :0.0
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