Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Although a human homolog of Chk 1 ( hChk 1 ) has recently been reported to be involved in the DNA damage checkpoint through phosphorylation of Cdc25A , B , and C , it is not known at which phase ( s ) of the cell cycle hChk 1 functions and how hChk 1 causes cell cycle arrest in response to DNA damage . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
The optimal motifs are similar for both kinases and most closely resemble the previously identified Chk 1 and hCds1 / Chk2 substrate target sequences in Cdc25C and Cdc25A , the regulation of which plays an important role in S and G ( 2 ) M arrest . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Certain stresses such as ultraviolet light stimulate the rapid and selective destruction of Cdc25A protein through a Chk 1 protein kinase dependent pathway . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Chk 1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition . ^^^ Here we show that the checkpoint kinase Chk 1 , but not Cds 1 ( Chk 2 ) , is activated transiently at the MBT in a maternal / zygotic gene product regulated manner and is essential for cell cycle elongation and Cdc25A degradation at this transition . ^^^ A constitutively active form of Chk 1 can phosphorylate Cdc25A in vitro and can target it rapidly for degradation in pre MBT embryos . ^^^ Intriguingly , for this degradation , however , Cdc25A also requires a prior Chk 1 independent phosphorylation at Ser 73 . ^^^ Thus , the physiological replication checkpoint is activated transiently at the MBT by developmental cues , and activated Chk 1 , only together with an unknown kinase , targets Cdc25A for degradation to ensure later development . . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Inhibition of cyclin dependent kinase 2 by the Chk 1 Cdc25A pathway during the S phase checkpoint activated by fludarabine : dysregulation by 7 hydroxystaurosporine . ^^^ 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 O14757	Pubmed	SVM Score :0.0
In addition , loss of Chk 1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase , and Chk 1 deficient cells failed to degrade Cdc25A after IR . ^^^ The IR induced S and G ( 2 ) checkpoints were partially restored in Chk 1 deficient cells when Cdc25A accumulation was interfered with . ^^^ Finally , Cdc25A was phosphorylated by Chk 1 in vitro on similar sites phosphorylated in vivo , including serine 123 . ^^^ These findings indicate that Chk 1 directly phosphorylates Cdc25A during an unperturbed cell cycle , and that phosphorylation of Cdc25A by Chk 1 is required for cells to delay cell cycle progression in response to double strand DNA breaks . . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Chk 1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation induced accelerated proteolysis of Cdc25A . ^^^ Here , we show that chemical or genetic ablation of human Chk 1 triggered supraphysiological accumulation of the S phase promoting Cdc25A phosphatase , prevented ionizing radiation ( IR ) induced degradation of Cdc25A , and caused radioresistant DNA synthesis ( RDS ) . ^^^ The basal turnover of Cdc25A operating in unperturbed S phase required Chk 1 dependent phosphorylation of serines 123 , 178 , 278 , and 292 . ^^^ IR induced acceleration of Cdc25A proteolysis correlated with increased phosphate incorporation into these residues generated by a combined action of Chk 1 and Chk 2 kinases . ^^^ Finally , phosphorylation of Chk 1 by ATM was required to fully accelerate the IR induced degradation of Cdc25A . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Chk 1 mediates S and G 2 arrests through Cdc25A degradation in response to DNA damaging agents . ^^^ The degradation of Cdc25A is abrogated by caffeine , which implicates Chk 1 as the potential mediator ( Mailand , N . , Falck , J . , Lukas , C . , Syljuasen , R . ^^^ Using a small interfering RNA that enables the specific elimination of Chk 1 expression , we show that the observed proteolysis of Cdc25A is mediated through Chk 1 . ^^^ Moreover , Cdc25A overexpression abrogates the Chk 1 mediated degradation and overcomes the doxorubicin induced G 2 arrest through dephosphorylation and activation of Cdc2 / Cdk1 in a dose dependent manner . ^^^ These results suggest that : ( a ) Cdc25A is involved in the G2 / M transition in addition to its commonly accepted effect on G1 / S progression , and ( b ) Chk 1 mediates both S and G 2 checkpoint and is thus a more ubiquitous cell cycle checkpoint mediator than previously thought . . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
In response to ionizing radiation , Cdc25A is phosphorylated by both Chk 1 and Chk 2 on Ser 123 . ^^^ Furthermore , we find that Cdc25A was phosphorylated by Chk 1 on Ser 75 in vitro and that the same site was also phosphorylated in vivo . ^^^ Taken together , these data strongly suggest that phosphorylation of Cdc25A on Ser 75 by Chk 1 and its subsequent degradation is required to delay cell cycle progression in response to UV induced DNA lesions . . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Phosphorylation by Chk 1 and Cds1 / Chk2 down regulates Cdc25A levels in response to genotoxic stresses . ^^^ Nevertheless , it remains unclear whether Chk 1 and Cds1 / Chk2 are uniquely responsible for regulating Cdc25A stability during interphase or if other kinase activities contribute . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Finally , CDC25A , CDC25B , a dominant negative CHK 1 , but not CDC25C or a dominant negative WEE 1 , stimulated histone H 3 phosphorylation after DNA damage . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
In non stressed conditions and in non mitotic cells , Cdc25A is unstable and its stability is regulated in a Chk 1 dependent manner . ^^^ We further show that Chk 1 kinase regulates Cdc25A stability after UV irradiation . ^^^ Similar to Chk 1 kinase , p 38 MAPK controls Cdc25A protein level after osmotic stress . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
PUVA induced rapid phosphorylation of the Chk 1 checkpoint kinase at Ser 345 and a concomitant decrease in Cdc25A levels . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Chk 1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14 3 3 binding . ^^^ The order and fidelity of cell cycle events in mammals is intimately linked to the integrity of the Chk 1 kinase Cdc25A phosphatase pathway . ^^^ Chk 1 phosphorylation targets Cdc25A for destruction and , as shown here , inhibits interactions between Cdc25A and its mitotic substrate cyclin B 1 Cdk1 . ^^^ Phosphorylation of Cdc25A on serine 178 and threonine 507 facilitates 14 3 3 binding , and Chk 1 phosphorylates both residues in vitro . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Consistent with Chk 1 being an Hsp 90 client , we also found that Chk 1 but not Chk 2 is destabilized in cells treated with the Hsp 90 inhibitor 17 allylamino 17 demethoxygeldanamycin ( 17 AAG ) . 17 AAG mediated Chk 1 loss blocked the ability of Chk 1 to target Cdc25A for proteolytic destruction , demonstrating that the Chk 1 signaling pathway was disrupted in the 17 AAG treated cells . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
In response to DNA damage or stalled replication , the ATM and ATR protein kinases activate the checkpoint kinases Chk 1 and Chk 2 , which leads to hyperphosphorylation of Cdc25A . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
SCFbeta TRCP links Chk 1 signaling to degradation of the Cdc25A protein phosphatase . ^^^ SCFbeta TRCP promotes Chk 1 dependent Cdc25A ubiquitination in vitro , and this involves serine 76 , a known Chk 1 phosphorylation site . ^^^ However , recognition of Cdc25A by beta TRCP occurs via a noncanonical phosphodegron in Cdc25A containing phosphoserine 79 and phosphoserine 82 , sites that are not targeted by Chk 1 . ^^^ These data indicate that Cdc25A turnover is more complex than previously appreciated and suggest roles for an additional kinase ( s ) in Chk 1 dependent Cdc25A turnover . . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
These studies suggest that in addition to targeting Cdc25A for degradation , Chk 1 may also function in cell cycle remodeling at the MBT by stabilizing Wee 1 until it is replaced by the somatic Wee 2 protein during gastrulation . . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
In response to DNA damage or to stalled replication , the activation of the ATM and ATR protein kinases leads to Chk 1 and Chk 2 activation and to Cdc25A hyperphosphorylation . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
ATR , Claspin and the Rad 9 Rad1 Hus 1 complex regulate Chk 1 and Cdc25A in the absence of DNA damage . ^^^ Chk 1 mediated phosphorylation of the Cdc25A phosphatase is required for the mammalian S phase checkpoint . ^^^ Here , we show that during physiological S phase the regulation of the Chk 1 Cdc25A pathway depends on ATR , Claspin , Rad 9 , and Hus 1 . ^^^ Human cells with chemically or genetically ablated ATR showed inhibition of Chk 1 dependent phosphorylation of Cdc25A , and they accumulated Cdc25A without external DNA damage . ^^^ Thus , the ATR Chk 1 Cdc25A pathway represents an integral part of physiological S phase progression , and interference with this mechanism undermines viability of somatic mammalian cells . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
In vertebrates , Chk 1 and Chk 2 phosphorylate Cdc25A at multiple N terminal sites and target it for rapid degradation in response to genotoxic stress . ^^^ Here we show that Chk 1 , but not Chk 2 , phosphorylates Xenopus Cdc25A at a novel C terminal site ( Thr 504 ) and inhibits it from C terminally interacting with various Cdk cyclin complexes , including Cdk 1 cyclin A , Cdk 1 cyclin B , and Cdk 2 cyclin E . ^^^ Strikingly , this inhibition , rather than degradation itself , of Cdc25A is essential for the Chk 1 induced cell cycle arrest and the DNA replication checkpoint in early embryos . 14 3 3 proteins bind to Chk 1 phosphorylated Thr 504 , but this binding is not required for the inhibitory effect of Thr 504 phosphorylation . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Slowing follows caffeine sensitive activation of the checkpoint kinase , Chk 1 ; degradation of the cell cycle phosphatase , Cdc25A ; and inhibitory phosphorylation of Cdc25C and cyclin dependent kinases ( Cdks ) . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
During normal cell cycle progression and after DNA damage phosphorylation by Chk 1 ( or Chk 2 ) triggers Cdc25A degradation via ubiquitin proteasome pathway . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
These observations suggest that although FdUrd induced S phase arrest and associated cdc25A degradation are impaired in HT 29 cells , signaling by ATM / ATR is intact upstream of chk 1 and chk 2 . ^^^
Interacting proteins: P30304 and O14757	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 . ^^^ Chk 1 elimination stabilizes the Cdc25A protein and results in the abrogation of the S checkpoint and resumption of DNA synthesis , which leads to excessive accumulation of double stranded DNA breaks . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Proteasome mediated degradation of Cdc25A and phosphorylation of Cdc25C were induced by Ara C treatment , presumably due to the activation of Chk 2 and Chk 1 , respectively . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
The findings of decreased Chk 1 activity and accumulation of Cdc25A , a protein targeted for degradation by Chk 1 , confirmed that Chk 1 function was impaired . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Disruption of CHK 1 function bypassed the checkpoint , as manifested by the increase in CDC25A , activation of CDC 2 , increase in histone H 3 phosphorylation , and reduction in cell survival after Adriamycin treatment . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
The checkpoint defect was traced to the ability of AKT to phosphorylate CHK 1 at serine 280 , since a nonphosphorylated mutant of CHK 1 ( S280A ) complemented the checkpoint defect and restored CDC25A degradation . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Furthermore , Chk 1 also phosphorylates Cdc25A on serine 123 which accelerates its degradation through the ubiquitin proteasome pathway and arrests cells in late G 2 phase after DNA damage . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Cytarabine , at concentrations as low as 30 nM , caused activating phosphorylation of Chk 1 , loss of the phosphatase Cdc25A , and S phase slowing . ^^^ Conversely , treatment with 100 to 300 nM 17 AAG for 24 hours caused Chk 1 depletion that was accompanied by diminished cytarabine induced S phase accumulation , decreased Cdc25A degradation , and enhanced cytotoxicity as measured by inhibition of colony formation and induction of apoptosis . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Beta TrCP binds to the DSG motif of human Cdc25A in a manner dependent on Chk 1 and other unknown kinases . ^^^ When analyzed by using Xenopus eggs , the binding of beta TrCP to the DDG motif is essential for the Chk 1 induced ubiquitination and degradation of Xenopus Cdc25A and also plays a role in the degradation of human Cdc25A . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
We found that radiosensitizing concentrations of gemcitabine induced accumulation of phosphorylated Chk 1 and Chk 2 and down regulation of Cdc25A in BxPC 3 ( 10 nmol / L ) , Panc 1 ( 100 nmol / L ) , A 549 ( 30 nmol / L ) , RKO ( 30 nmol / L ) , and SW 620 ( 30 nmol / L ) cells . ^^^ Depletion of Chk 1 from Panc 1 cells prevented the down regulation of Cdc25A in response to gemcitabine . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Interestingly , CDC25A regulation was Chk 1 dependent in these cells as suggested by siRNA mediated down regulation of this protein . ^^^ Altogether , our data show that in leukemic cells adhesion to fibronectin increases CDC25A expression through proteasome and Chk 1 dependent mechanisms , resulting in enhanced proliferation . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Importantly , expression of wild type Chk 1 , but not kinase dead Chk 1 , inhibits the camptothecin induced increase in Cdc25A activity . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Chk 1 executes these functions , in part , by targeting the Cdc25A protein phosphatase for ubiquitin mediated proteolysis . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
Here we show that depletion of DNMT 1 with either antisense or small interfering RNA ( siRNA ) specific to DNMT 1 activates a cascade of genotoxic stress checkpoint proteins , resulting in phosphorylation of checkpoint kinases 1 and 2 ( Chk 1 and 2 ) , gammaH2AX focus formation , and cell division control protein 25a ( CDC25a ) degradation , in an ataxia telangiectasia mutated Rad 3 related ( ATR ) dependent manner . siRNA knockdown of ATR blocks the response to DNMT 1 depletion ; DNA synthesis continues in the absence of DNMT 1 , resulting in global hypomethylation . ^^^
Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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Interacting proteins: P30304 and O14757	Pubmed	SVM Score :0.0
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