| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.90718595 |
| Cdc25A , a phosphatase essential for G 1 S transition , associates with , dephosphorylates , and activates the cell cycle kinase cyclin E cdk 2 . p21CIP1 and p 27 are cyclin dependent kinase ( cdk ) inhibitors induced by growth suppressive signals such as p 53 and transforming growth factor beta ( TGF beta ) . 0.90718595^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The latter resulted from the rapid alpha interferon mediated elimination of cdc25A , a phosphatase that is required for antagonism of negative tyrosine phosphorylation of cdk 2 in cyclin cdk complexes . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Aloesin up regulates cyclin E / CDK2 kinase activity via inducing the protein levels of cyclin E , CDK 2 , and CDC25A in SK HEP 1 cells . ^^^ The data showed that aloesin increased the levels of cyclin E , CDK 2 , and CDC25A in SK HEP 1 cells . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The results from immunoblottings show that the down regulation of cyclin E dependent kinase activity is related to increased protein levels of p21Cip / WAF1 and to decreased protein levels of cyclin E , CDK 2 , and CDC25A . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Treatment of MCF 7 cells with E 2 also induced cdc25A phosphatase protein , which was accompanied by increased cdk 2 and cdk 4 proteins containing unphosphorylated tyrosine residues . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The surface positioning of subfamily specific conserved residues allows us to predict the sites of interaction with Cdk 2 , a physiological target of Cdc25a . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| When Myc induced cells are deprived of serum growth factors , they rapidly become apoptotic with the onset of apoptosis preceded by a large , transient increase in cdk 2 kinase activity that is associated with the induction of cdc25A phosphatase and the later accumulation of p27Kip1 kinase inhibitor . ^^^ Surprisingly , serum starvation in the absence of myc overexpression , ( which leads to quiescence instead of apoptosis ) also causes a marked transient elevation in cdk 2 kinase activity , an induction of cdc25A and a delayed increase in p27Kip1 . ^^^ Transient elevations in cdk 2 kinase activity and cdc25A abundance are required for cell cycle progression , but it is evident that these changes also precede entry to either apoptosis or quiescence in serum starved cells . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk 2 . ^^^ The cdc25A phosphatase removes inhibitory phosphates from threonine 14 and tyrosine 15 of cyclin dependent kinase 2 ( cdk 2 ) in vitro , and it is therefore widely assumed that cdc25A positively regulates cyclin E and A associated cdk 2 activity at the G 1 to S phase transition of the mammalian cell division cycle . ^^^ Paradoxically , tyrosine phosphorylation of cdk 2 increased considerably as cells entered S phase , and cdc25A overexpression potentiated rather than diminished this effect . ^^^ At face value , these results are inconsistent with the hypothesis that cdc25A acts directly on cdk 2 to activate its S phase promoting function . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cdc25A tyrosine phosphatase is an activator of the cdk 2 cyclin E complex which allows for cell cycle progression . ^^^ As expected , we found TNFalpha mediated Cdc25A down regulation to inhibit Cdk 2 activity . ^^^ TNFalpha induced apoptosis is not accompanied by cell cycle arrest which may be due to constitutive c Myc expression , although Cdc25A and Cdk 2 activity is also down regulated . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Over expression of CDK 2 , CDK 6 , CDC25A and cyclin A was confirmed in melanoma cell lines . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Rather , expression of cyclin A , which regulates cdk 2 activity , and the cdc25A and cdc25B phosphatases , which are thought to activate cdk 2 , was significantly reduced at both the RNA and protein levels in response to E 2 expression . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The development of hypertrophy does not involve regulation of either cdk 2 , cyclin E , or cdc25A protein abundances , or the abundance of p 27 ( Kip 1 ) or p 21 in formed complexes . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Overexpression of Cdc25A in the inducible system , however , leads to a premature activation of both cyclin E Cdk 2 and cyclin A Cdk 2 complexes , while no effect of cyclin D dependent kinases is observed . ^^^ Furthermore , Cdc25A overexpression induces a tyrosine dephosphorylation of Cdk 2 . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Apoptosis was accompanied by sustained c Myc expression , concurrent down regulation of cdc25A mRNA and protein , and by inhibition of Cdk 2 activity . ^^^ Both Cdk 2 and cdc25A are G 1 phase specific genes and Cdk 2 is the target of Cdc25A . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The loss of Cdc25A was associated with an increase in the phosphotyrosylation of cyclin E associated cdk 2 , which may contribute to cell cycle arrest during differentiation . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cdk 7 and Cdc25A independent dephosphorylation of Cdk 2 during phorbol ester mediated cell cycle arrest in U 937 cells . ^^^ Dephosphorylation of cdk 2 was not associated with cdk 7 and cdc25A activity in phorbol ester treated cells . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the protein kinase complexes consisting of cyclin A 1 and either Cdc 2 or Cdk 2 phosphorylate both Cdc25A and Cdc25C in vitro . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Here we show that Cdc25A is overexpressed in primary breast tumors and that such overexpression is correlated with higher levels of cyclin dependent kinase 2 ( Cdk 2 ) enzymatic activity in vivo . ^^^ Furthermore , in the breast cancer cell line MCF 7 , Cdc25A activity is necessary for both the activation of Cdk 2 and the subsequent induction of S phase entry . ^^^ These data suggest that overexpression of Cdc25A contributes to the biological behavior of primary breast tumors and that both Cdc25A and Cdk 2 are suitable therapeutic targets in early stage breast cancer . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| A loss of Cdc25A expression was associated with an increased inhibitory phosphotyrosine content of cyclin E and cyclin A associated cdk 2 and may also contribute to G 1 arrest following UVB irradiation . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The inhibition of cyclin E cdk 2 in senescent HMECs was accompanied by increased inhibitory phosphorylation of cdk 2 , in association with a progressive loss of Cdc25A . ^^^ Recombinant Cdc25A strongly reactivated cyclin E cdk 2 from senescent HMECs suggesting that reduction of Cdc25A contributes to cyclin E cdk 2 inhibition and G 1 arrest at senescence . ^^^ Although ectopic expression of Cdc25A failed to extend the lifespan of HMECs , the exogenous Cdc25A appeared to lack activity in these cells , since it neither shortened the G 1 to S phase interval nor activated cyclin E cdk 2 . ^^^ In contrast , in the breast cancer derived MCF 7 line , Cdc25A overexpression increased both cyclin E cdk 2 activity and the S phase fraction . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| On the other hand , the arrest was accompanied by down regulation of kinase activity of Cdk 2 , although the total protein levels of Cdk 2 and its activator Cdc25A were unaffected . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Inhibition of Cdc25A activity in p 16 ( INK4a ) expressing cells was associated with depressed Cdk 2 activity and was reversed in vivo and in vitro by active Cdk 2 . ^^^ Transfection of MCF 7 cells with a dominant negative Cdk 2 construct inhibited the E ( 2 ) dependent activation of ectopic Cdc25A . ^^^ Supporting a role for Cdc25A in estrogen action , antisense CDC25A oligonucleotides inhibited estrogen induced Cdk 2 activation and DNA synthesis . ^^^ In addition , inactive cyclin E Cdk 2 complexes from p 16 ( INK4a ) expressing , estrogen treated cells were activated in vitro by treatment with recombinant Cdc25A and in vivo in cells overexpressing Cdc25A . ^^^ The results demonstrate that functional association of cyclin D 1 Cdk4 complexes is required for Cdk 2 activation in MCF 7 cells and that Cdk 2 activity is , in turn , required for the in vivo activation of Cdc25A . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Particular emphasis is put on the emerging parallel yet cooperative pathways of retinoblastoma protein ( pRB ) E2F and Myc , their convergence to control the activity of the cyclin dependent kinase 2 ( Cdk 2 ) at the G1 / S boundary , as well as the two waves of checkpoint responses at G1 / S : the rapid pathway ( s ) leading to Cdc25A degradation , and the delayed p 53 p21 cascade , both silencing the Cdk 2 activity upon DNA damage . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The Cdc25A phosphatase activates the cyclin dependent kinase 2 ( Cdk 2 ) needed for DNA synthesis , but becomes degraded in response to DNA damage or stalled replication . ^^^ An IR induced loss of Cdc25A protein prevents dephosphorylation of Cdk 2 and leads to a transient blockade of DNA replication . ^^^ We also show that tumour associated Chk 2 alleles can not bind or phosphorylate Cdc25A , and that cells expressing these Chk 2 alleles , elevated Cdc25A or a Cdk 2 mutant unable to undergo inhibitory phosphorylation ( Cdk2AF ) fail to inhibit DNA synthesis when irradiated . ^^^ These results support Chk 2 as a candidate tumour suppressor , and identify the ATM Chk 2 Cdc25A Cdk 2 pathway as a genomic integrity checkpoint that prevents radioresistant DNA synthesis . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Here , we discuss how estrogens exert control over several key G 1 phase cell cycle regulators , namely cyclin D 1 , Myc , Cdk 2 , Cdk 4 , Cdk inhibitors and Cdc25A . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Expression of cdc25A , a phosphatase that activates cdk 2 , was reduced during 24 hr exposure to gnidimacrin . ^^^ These results suggest that gnidimacrin exerts antitumor activity through suppression of cdc25A and inhibition of cdk 2 activity . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| In Xenopus embryos , cell cycle elongation and degradation of Cdc25A ( a Cdk 2 Tyr15 phosphatase ) occur naturally at the midblastula transition ( MBT ) , at which time a physiological DNA replication checkpoint is thought to be activated by the exponentially increased nucleo cytoplasmic ratio . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation studies demonstrated complexes of Cdk 2 , Cdc25A , and Chk 1 . ^^^ Under these conditions , the kinase activity of Chk 1 was reduced , Cdc25A phosphatase activity was increased , the level of Tyr ( 15 ) phosphorylation of Cdk 2 was reduced , and the kinase activity associated with immunoprecipitates of Cdk 2 and cyclin A was reactivated . ^^^ Thus , the DNA damage induced by F ara A initiated a hierarchical regulatory cascade through Chk 1 and Cdc25A that resulted in Cdk 2 inhibition , affecting an S phase checkpoint that was dysregulated by UCN 01 . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The primary module , which includes the interactions between cyclin E ( CycE ) , cyclin dependent kinase 2 ( CDK 2 ) , and protein phosphatase CDC25A , exhibits dynamics such as limit cycle , bistability , and excitable transient . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| DNA replication in higher eukaryotes requires activation of a Cdk 2 kinase by Cdc25A , a labile phosphatase subject to further destabilization upon genotoxic stress . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Furthermore , increased nuclear p 21 levels and reduced expression of Cdc25A phosphatase coincided with decreases in Cdk 2 activation and hepatocyte progression into S phase . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Transfection with dominant negative Cdk mutants demonstrated that only a Cdk 2 mutant increased Cdc25A protein levels ; Cdk 1 and Cdk 3 mutants had no effect . ^^^ These results demonstrate Cdk 2 kinase activity contributes to the labile nature of Cdc25A during interphase and redefine the nature of the Cdc25A Cdk 2 autoamplification feedback loop . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cdc42V12 promotes Cdk 2 activation by selectively inducing cyclin E expression without affecting other regulatory proteins such as the p 27 Cdk inhibitor or Cdc25A . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cdk 2 is activated in the nucleus by Cdk activating kinase through Thr 160 phosphorylation and by cdc25A phosphatase via Thr 14 and Tyr 15 dephosphorylation . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Novel observations modify the current model of the sequential CDK 2 activation process : ( 1 ) Tyr 15 phosphorylation induced by serum was not restricted to cyclin bound CDK 2 ; ( 2 ) Thr 160 phosphorylation engaged the entirety of Tyr 15 phosphorylated CDK 2 associated not only with a cyclin but also with p 27 and p 21 , suggesting that Cip / Kip proteins do not prevent CDK 2 activity by impairing its phosphorylation by CAK ; ( 3 ) the potentially active CDK 2 phosphorylated at Thr 160 but not Tyr 15 represented a tiny fraction of total CDK 2 and a minor fraction of cyclin A bound CDK 2 , underscoring the rate limiting role of Tyr 15 dephosphorylation by cdc25A . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cdc25A is at least 20 fold more sensitive to bpV inhibition than hVH2 / DSP4 , and 3 to 10 fold more sensitive than TCPTP and LAR . bpV inhibition of Cdc25A in cells leads to CDK 2 inactivation and hypophosphorylation Rb , resulting in G 1 S arrest and induction of p 53 independent apoptosis . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The most consistent effect of cAMP was to block both FBS and DeltaRaf 1 : ER induced expression of Cdc25A and cyclin A , two important activators of CDK 2 . ^^^ When CDK 2 activity was bypassed by activation of the ER E2F1 fusion protein , cAMP no longer inhibited expression of Cdc25A or cyclin A but still inhibited DNA synthesis . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cdc25A is required for S phase entry and dephosphorylates tyrosine 15 phosphorylated Cdk 1 ( Cdc 2 ) and Cdk 2 , positive regulators of cell division . ^^^ Depletion of beta TRCP stabilizes Cdc25A , leading to hyperactive Cdk 2 activity . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| This results from the phosphorylation and subsequent inactivation of two inhibitory kinases ( WEE 1 and MYT 1 ) that tonically suppress CDK 2 and CDC 2 activity and activation of a phosphatase ( CDC25A ) that increases CDK 2 activity . . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
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: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| In CCl 39 cells this promoted a sustained G 1 arrest that correlated with decreased expression of cyclin D 1 and Cdc25A , increased expression of p21CIP1 and inhibition of CDK 2 activity . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| However , irradiation of E1A + E1B 19 kDa transformed cells induces no changes in CAK ( Cdk 7 associated ) kinase activity and in the protein level of Cdc25A phosphatase , which are responsible for activating Thr 160 phosphoralation and Tyr 15 dephosphorylation on Cdk 2 . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Here , we demonstrated that STI 571 also induces growth arrest by activating the Chk 2 Cdc25A Cdk 2 axis , a pathway complementary to p 53 in the activation of G ( 1 ) / S cell cycle checkpoint . ^^^ In vitro exposure to STI 571 of 32D murine myeloid progenitor cell clones transducing a temperature sensitive p 210 bcr abl construct was associated with Chk 2 phosphorylation and activation , Cdc25A degradation and persistent Cdk 2 inhibitory phosphorylation , preventing , in turn , cell transition to and progression throughout the S phase of cell cycle . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ATM and ATR with caffeine or specific neutralizing antibodies , or upregulation of Cdk 2 or Cdc 7 , promoted rapid and synchronous origin firing ; conversely , inhibition of Cdc25A slowed DNA replication . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Cyclin D 1 , cdk 2 , and cdc25A protein levels were increased , and p 15 ( Ink4b ) and p 27 ( Kip 1 ) protein levels were decreased . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| The affected pathways are those mediated by p 53 and p 21 and by ATM , Chk 2 , Cdc25A , and Cdk 2 . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| Chk 1 downregulation abrogates this arrest and dramatically sensitizes tumor cells to the cytotoxic effects of 5 FU . 5 FU confers S phase arrest through Chk 1 mediated Cdc25A proteolysis leading to inhibition of Cdk 2 . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| In addition , SB 203580 affected neither Cdc25A phosphatase expression nor Cdk 2 Tyr 15 phosphorylation . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| In addition , increased p 27 stability and retention in the nucleus and decreased levels of the cdc25a phosphatase contributed to a significant loss of cdk 2 kinase activity . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| MATERIALS AND METHODS : MTT assay , Western blot analysis of COX 2 and cell cycle related molecules in the G 1 phase ( Rb , CDC25A , cyclin D 1 ) , and CDK 2 kinase assay were performed on chenodeoxycholic acid ( CDCA ) exposure to ESCC cell lines ( TE2R , TE 3 , TE 13 , TE 15 ) . ^^^ Only a low dose of bile acid induced the expression of cyclin D 1 and CDC25A and showed high Rb phosphorylation and high CDK 2 kinase activity . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| This reduction in Cdk 2 activity was associated with a decrease in the expression of Cdk 7 , Cdc25A , and cyclin A . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| RNA interference mediated depletion and chromatin immunoprecipitation assays show that endogenous ACTR directly controls the expression of genes important for initiation of DNA replication , which include cdc 6 , cdc25A , MCM 7 , cyclin E , and Cdk 2 . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| As a result of its action , tyrosine phosphorylation of the cellular Cdc25A substrates Cdk 2 and Cdk 4 was induced . ^^^ |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P30304 and P24941 |
Pubmed |
SVM Score :0.0 |
| NA |
|