Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A

Teixeira LK, Reed SI. Ubiquitin ligases and cell cycle control. Annu Rev Biochem. 2013;82():387–414. doi: 10.1146/annurev-biochem-060410-105307. PMID: 23495935.; Piao S, Lee SJ, Xu Y, Gwak J, Oh S, Park BJ, Ha NC. CK1e targets Cdc25A for ubiquitin-mediated proteolysis under normal conditions and in response to checkpoint activation. Cell Cycle. 2011 Feb 01;10(3):531–7. doi: 10.4161/cc.10.3.14757. PMID: 21252624.; Honaker Y, Piwnica-Worms H. Casein kinase 1 functions as both penultimate and ultimate kinase in regulating Cdc25A destruction. Oncogene. 2010 Jun 10;29(23):3324–34. PMID: 20348946; PMCID: PMC2883652.; Melixetian M, Klein DK, Sørensen CS, Helin K. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat Cell Biol. 2009 Oct;11(10):1247–53. doi: 10.1038/ncb1969. PMID: 19734889.; Kang T, Wei Y, Honaker Y, Yamaguchi H, Appella E, Hung MC, Piwnica-Worms H. GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers. Cancer Cell. 2008 Jan;13(1):36–47. PMID: 18167338; PMCID: PMC2276649.; Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature. 2003 Nov 06;426(6962):87–91. doi: 10.1038/nature02082. PMID: 14603323.; Goloudina A, Yamaguchi H, Chervyakova DB, Appella E, Fornace AJ, Bulavin DV. Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint. Cell Cycle. 2003 Sep;2(5):473–8. PMID: 12963847.; Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ, Harper JW. SCFß-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 2003 Jan 01;17(24):3062–74. doi: 10.1101/gad.1157503.; Bartek J, Lukas J. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr Opin Cell Biol. 2001 Dec;13(6):738–47. doi: 10.1016/s0955-0674(00)00280-5. PMID: 11698191.; Falck J, Mailand N, Syljuåsen RG, Bartek J, Lukas J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature. 2001 Apr 12;410(6830):842–7. doi: 10.1038/35071124. PMID: 11298456.; Molinari M, Mercurio C, Dominguez J, Goubin F, Draetta GF. Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis. EMBO Reports. 2000 Jul;1(1):71–9. doi: 10.1093/embo-reports/kvd018.; Mailand N, Falck J, Lukas C, Syljuâsen RG, Welcker M, Bartek J, Lukas J. Rapid destruction of human Cdc25A in response to DNA damage. Science. 2000 May 26;288(5470):1425–9. doi: 10.1126/science.288.5470.1425. PMID: 10827953.; Bernardi R, Liebermann DA, Hoffman B. Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation. Oncogene. 2000 May 11;19(20):2447–54. doi: 10.1038/sj.onc.1203564. PMID: 10828887.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.3.2.27 RING-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
2.3.2.32 cullin-RING-type E3 NEDD8 transferase [E2 NEDD8-conjugating enzyme]-S-[NEDD8-protein]-yl-L-cysteine:[cullin] [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.21 polo kinase ATP:protein phosphotransferase (spindle-pole-dependent)
2.7.11.26 tau-protein kinase ATP:[tau-protein] O-phosphotransferase
3.1.3.48 protein-tyrosine-phosphatase protein-tyrosine-phosphate phosphohydrolase


Proteins

Protein ID name full name