Reactome | CHEK1 phosphorylates CHEK2-phosphorylated CDC25A

CHEK1 phosphorylates CHEK2-phosphorylated CDC25A

Stable Identifier

R-HSA-9943678

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

3/5

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CHEK1 phosphorylates CHEK2-phosphorylated CDC25A

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Although CHEK2 depletion stabilizes CDC25A, additional CHEK1 depletion further increases CDC25A stability (Jin et al. 2008). As the phosphorylation patterns of CDC25A by CHEK1 and CHEK2 partially overlap (Sorensen et al. 2003, Jin et al. 2008), and as CHEK1 phosphorylates CDC25A on S76 (Goloudina et al. 2003, Hassepass et al. 2003, Jin et al. 2008, Kang et al. 2008) while CHEK2 does not (Jin et al. 2008), and as S76 phosphorylation is required for SCF-BTrCP-mediated ubiquitination of CDC25A (Jin et al. 2003), it is plausible that CHEK1 phosphorylates S76 on CHEK2-phosphorylated CDC25A. CHEK1 was also reported to phosphorylate CDC25A on S279 (Sorensen et al. 2003), a site not reported to be phosphorylated by CHEK2, so it is assumed that S279 of CHEK2-phosphorylated CDC25A can also undergo CHEK1-mediated phosphorylation.

Literature References

PubMed ID	Title	Journal	Year
12676583	Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A Sørensen, CS, Syljuåsen, RG, Falck, J, Schroeder, T, Rönnstrand, L, Khanna, KK, Zhou, BB, Bartek, J, Lukas, J	Cancer Cell	2003
12759351	Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint Hassepass, I, Voit, R, Hoffmann, I	J Biol Chem	2003
18480045	Differential roles for checkpoint kinases in DNA damage-dependent degradation of the Cdc25A protein phosphatase Jin, J, Ang, XL, Ye, X, Livingstone, M, Harper, JW	J Biol Chem	2008
12963847	Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint Goloudina, A, Yamaguchi, H, Chervyakova, DB, Appella, E, Fornace, AJ, Bulavin, DV	Cell Cycle	2003