Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
The ATM Chk 2 Cdc25A checkpoint pathway guards against radioresistant DNA synthesis . ^^^ Here we report a functional link between ATM , the checkpoint signalling kinase Chk2 / Cds1 ( Chk 2 ) and Cdc25A , and implicate this mechanism in controlling the S phase checkpoint . ^^^ We show that IR induced destruction of Cdc25A requires both ATM and the Chk 2 mediated phosphorylation of Cdc25A on serine 123 . ^^^ 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 O96017	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
However , downregulation of MDC 1 does not abolish the ionizing radiation induced phosphorylation of NBS 1 , CHK 2 and SMC 1 , or the degradation of CDC25A . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
Mutational analyses using GST linked Cdc25A containing serine 123 revealed that residues at positions 5 and 3 are critical determinants for the recognition of the Chk 2 substrate . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
In response to ionizing radiation , Cdc25A is phosphorylated by both Chk 1 and Chk 2 on Ser 123 . ^^^
Interacting proteins: P30304 and O96017	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 O96017	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 O96017	Pubmed	SVM Score :0.0
In response to DNA damage , the cell cycle checkpoint kinase 2 ( CHEK 2 ) may phosphorylate p 53 , Cdc25A and Cdc25C , and regulate BRCA 1 function , leading to cell cycle arrest and DNA repair . ^^^
Interacting proteins: P30304 and O96017	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 O96017	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 . ^^^ Chk 2 and Cdc25A are both components of a complex network that integrates signals involved in regulated cell cycle progression , DNA repair and cell decision between life or death . ^^^ Chk 2 gene mutations or decreased expression , leading to its protein loss of function on Cdc25A target , and Cdc25A overexpression have been linked to poor prognosis of human cancers . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
However , ATM dependent phosphorylation and activation of the checkpoint kinase CHK 2 and subsequent degradation of its downstream target , CDC25A , was abrogated in cells lacking mismatch repair . ^^^
Interacting proteins: P30304 and O96017	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 . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
MRK depletion by RNA interference resulted in defective S and G ( 2 ) checkpoints induced by IR that were accompanied by reduced Chk 2 phosphorylation and delayed Cdc25A degradation . ^^^ Thus , in response to IR MRK controls two independent pathways : the Chk 2 Cdc25A pathway leading to cell cycle arrest and the p38gamma MAPK pathway . . ^^^
Interacting proteins: P30304 and O96017	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 O96017	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 O96017	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 . ^^^ In ES cells , Chk 2 kinase is not intranuclear as in somatic cells but is sequestered at centrosomes and is unavailable to phosphorylate Cdc25A phosphatase and cause its degradation . ^^^ Although ectopic expression of Chk 2 does not rescue the p53 / p21 pathway , its expression is sufficient to allow it to phosphorylate Cdc25A , activate downstream targets , restore a G ( 1 ) arrest , and protect the cell from apoptosis . . ^^^
Interacting proteins: P30304 and O96017	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 O96017	Pubmed	SVM Score :0.0
Analysis of CDC25A degradation , a downstream target of CHK 2 , suggests that some compensation occurs to allow normal degradation of CDC25A . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
Moreover , the defects in Chk 2 ( T 68 ) phosphorylation in STAT 1 deficient cells also correlated with reduced degradation of Cdc25A compared with STAT 1 expressing cells after DNA damage . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
Wt Chk 2 created a pre MBT checkpoint due to degradation of Cdc25A and phosphorylation of cyclin dependent kinases . ^^^
Interacting proteins: P30304 and O96017	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 . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
Functionally , Chk 2 can activate both apoptosis ( via p 53 , E2F1 and PML ) and cell cycle checkpoint ( via Cdc25A and Cdc25C , p 53 , and BRCA 1 ) . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
Chk 2 transmits signals from upstream phosphatidylinositol 3 ' kinase like kinases to effector substrates including p 53 , Brca 1 , Cdc25A , and Cdc25C . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
Cellular exposure to cytotoxic concentration of SN 38 , the active metabolite of irinotecan ( 0 . 1 microM ) alone and in combination with noncytotoxic concentration of MSC ( 10 microM ) did not result in additional enhancement of chk 2 phosphorylation and downregulation of specific DNA replication associated proteins , cdc 6 , MCM 2 , cdc25A , nor increase in PARP cleavage , caspase activation and the 30 300 kb DNA fragmentation induced by SN 38 treatment . ^^^
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA
Interacting proteins: P30304 and O96017	Pubmed	SVM Score :0.0
NA