PubMed 12676925

Using a small interfering RNA that enables the specific elimination of Chk1 expression, we show that the observed proteolysis of Cdc25A is mediated through Chk1. Moreover, Cdc25A overexpression abrogates the Chk1-mediated degradation and overcomes the doxorubicin-induced G2 arrest through dephosphorylation and activation of Cdc2/Cdk1 in a dose-dependent manner ... from full text, H1299 cells and tyrosine 15 phosphorylation of CDC2

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
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e45600e3fa
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
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e45600e3fa
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PubMed 15798217

beta-TrCP2 siRNA also inhibits Smad3-induced Cdc25A degradation.

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
694d100f61
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
694d100f61
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PubMed 18285820

The consequential loss of CDC25A results in G1/S arrest, due to the inefficient loading of CDC45 at the origin of replication. In addition, activated ATM, ATR, DNA–PK, Chk2, and Chk1 all aid in the phosphorylation and activation of p53, a key player in DNA-damage checkpoints. Activated p53 transactivates p21, which inhibits two G1/S-promoting cyclin-dependent kinases (CDKs), CDK2 and CDK4.

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
762f8f4129
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
762f8f4129
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PubMed 12801928

Transfection with dominant-negative Cdk mutants demonstrated that only a Cdk2 mutant increased Cdc25A protein levels; Cdk1 and Cdk3 mutants had no effect. The increased Cdc25A protein levels were the result of an increase in the half-life of the protein

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
5abf4edf37
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
5abf4edf37
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PubMed 16633365

beta-TRCP is a versatile F-box protein that recognizes several cell-cycle regulators EMI1-2, WEE1A and CDC25A-B in addition to its classical substrates, beta-catenin and IkappaB. In some cancers, beta-TRCP mutation or overexpression is found.

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
7256b2837c
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
7256b2837c
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PubMed 12759351

phosphorylation of Cdc25A on Ser-75 by Chk1 and its subsequent degradation is required to delay cell cycle progression in response to UV-induced DNA lesions.

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
ef5c8a2a85
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
ef5c8a2a85
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PubMed 12411508

Mitotic stabilization of Cdc25A reflects its phosphorylation on Ser17 and Ser115 by cyclin B-Cdk1, modifications required to uncouple Cdc25A from its ubiquitin-proteasome-mediated turnover

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
d97e12cbf1
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
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d97e12cbf1
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PubMed 14681206

Depletion of beta-TRCP stabilizes Cdc25A, leading to hyperactive Cdk2 activity. SCFbeta-TRCP promotes Chk1-dependent Cdc25A ubiquitination in vitro, and this involves serine 76, a known Chk1 phosphorylation site.

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
27c3e409f7
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
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27c3e409f7
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PubMed 12676583

The basal turnover of Cdc25A operating in unperturbed S phase required Chk1-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 Chk1 and Chk2 kinases. Finally, phosphorylation of Chk1 by ATM was required to fully accelerate the IR-induced degradation of Cdc25A ... from full text, U2OS cells and ATM-dependent CHEK1 phosphorylation at S317 and S345

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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
cb6914eac9
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deg(p(RGD:Cdc25a)) directlyDecreases p(RGD:Cdc25a)
Hash
cb6914eac9
Networks

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of the open source project, PyBEL. Please feel free to contact us here to give us feedback or report any issues.