CDC25A

Cell division cycle 25 homolog A (S. pombe)
PDB rendering based on 1c25.
Available structures PDB 1c25
Identifiers
Symbols	CDC25A; CDC25A2
External IDs	OMIM: 116947 MGI: 103198 HomoloGene: 1355 GeneCards: CDC25A Gene
EC number	3.1.3.48
Gene Ontology Molecular function • phosphoprotein phosphatase activity • phosphoprotein phosphatase activity • protein tyrosine phosphatase activity • protein binding • hydrolase activity Cellular component • intracellular • nucleus • nucleoplasm • nucleoplasm • cytoplasm • cytosol Biological process • cell cycle checkpoint • regulation of cyclin-dependent protein kinase activity • G1/S transition of mitotic cell cycle • S phase of mitotic cell cycle • G2/M transition of mitotic cell cycle • mitotic cell cycle • DNA replication • mitosis • cell proliferation • cellular response to UV • cell division Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	993	12530
Ensembl	ENSG00000164045	ENSMUSG00000032477
UniProt	P30304	P48964
RefSeq (mRNA)	NM_001789.2	NM_007658.3
RefSeq (protein)	NP_001780.2	NP_031684.3
Location (UCSC)	Chr 3: 48.2 – 48.23 Mb	Chr 9: 109.78 – 109.8 Mb
PubMed search	[1]	[2]

Cell division cycle 25 homolog A (S. pombe), also known as CDC25A, is a mammalian gene.

CDC25A is a member of the CDC25 family of dual-specificity phosphatases.

Dual-specificity protein phosphatases remove phosphate groups from phosphorylated tyrosine and serine/threonine residues. They represent a subgroup of the tyrosine phosphatase family (as opposed to the serine/threonine phosphatase family.)

All mammals examined to date have three homologues of the S. pombe Cdc25 gene, designated Cdc25A, Cdc25B, and Cdc25C. In contrast, some invertebrates harbour 2 (e.g., Drosophila String and Twine) or four (e.g., C. elegans Cdc-25.1 - Cdc-25.4) homologues. CDC25A is required for progression from G1 to the S phase of the cell cycle, but also plays roles in later cell cycle events. In particular, it is stabilized in metaphase cells and is degraded upon metaphase exit akin to Cyclin B. It is competent to activate the G1/S cyclin-dependent kinases CDK4 and CDK2 by removing inhibitory phosphate groups from adjacent tyrosine and threonine residues; it can also activate Cdc2 (Cdk1), the principal mitotic Cdk.

Cdc25A in Checkpoints and Cancer CDC25A is specifically degraded in response to DNA damage, resulting in cell cycle arrest. Thus, this degradation represents one axis of a DNA damage checkpoint, complementing induction of p53 and p21 in the inhibition of Cdks. CDC25A is considered an oncogene, as it can cooperate with oncogenic ras to transform rodent fibroblasts, and it is overexpressed in tumours from a variety of tissues, including breast and head & neck tumours. It is a target of the E2F family of transcription factors. Therefore, its overexpression is a common consequence of dysregulation of the p53-p21-Cdk axis in carcinogenesis.

Interactions

CDC25A has been shown to interact with ASK1, Epidermal growth factor receptor, C-Raf, CHEK1, Cyclin E1, PIM1 and YWHAB.

Further reading

• Parsons R (1998). "Phosphatases and tumorigenesis". Current opinion in oncology 10 (1): 88–91. doi:10.1097/00001622-199801000-00014. PMID 9466490. 
• Kerkhoff E, Rapp UR (1998). "Cell cycle targets of Ras/Raf signalling". Oncogene 17 (11 Reviews): 1457–62. doi:10.1038/sj.onc.1202185. PMID 9779991. 
• Nilsson I, Hoffmann I (2000). "Cell cycle regulation by the Cdc25 phosphatase family". Progress in cell cycle research 4: 107–14. PMID 10740819. 
• Galaktionov K, Beach D (1992). "Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins". Cell 67 (6): 1181–94. doi:10.1016/0092-8674(91)90294-9. PMID 1836978. 
• Conklin DS, Galaktionov K, Beach D (1995). "14-3-3 proteins associate with cdc25 phosphatases". Proc. Natl. Acad. Sci. U.S.A. 92 (17): 7892–6. doi:10.1073/pnas.92.17.7892. PMC 41252. PMID 7644510. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41252. 
• Galaktionov K, Lee AK, Eckstein J, et al. (1995). "CDC25 phosphatases as potential human oncogenes". Science 269 (5230): 1575–7. doi:10.1126/science.7667636. PMID 7667636. 
• Galaktionov K, Jessus C, Beach D (1995). "Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation". Genes Dev. 9 (9): 1046–58. doi:10.1101/gad.9.9.1046. PMID 7744247. 
• Demetrick DJ, Beach DH (1994). "Chromosome mapping of human CDC25A and CDC25B phosphatases". Genomics 18 (1): 144–7. doi:10.1006/geno.1993.1440. PMID 8276402. 
• Xu X, Burke SP (1996). "Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25". J. Biol. Chem. 271 (9): 5118–24. doi:10.1074/jbc.271.9.5118. PMID 8617791. 
• Tiefenbrun N, Melamed D, Levy N, et al. (1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Mol. Cell. Biol. 16 (7): 3934–44. PMC 231390. PMID 8668211. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231390. 
• Huang TS, Shu CH, Yang WK, Whang-Peng J (1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis". Cancer Res. 57 (14): 2974–8. PMID 9230211. 
• Fauman EB, Cogswell JP, Lovejoy B, et al. (1998). "Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A". Cell 93 (4): 617–25. doi:10.1016/S0092-8674(00)81190-3. PMID 9604936. 
• Coqueret O, Bérubé G, Nepveu A (1998). "The mammalian Cut homeodomain protein functions as a cell-cycle-dependent transcriptional repressor which downmodulates p21WAF1/CIP1/SDI1 in S phase". EMBO J. 17 (16): 4680–94. doi:10.1093/emboj/17.16.4680. PMC 1170797. PMID 9707427. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170797. 
• Iavarone A, Massagué J (1999). "E2F and Histone Deacetylase Mediate Transforming Growth Factor β Repression of cdc25A during Keratinocyte Cell Cycle Arrest". Mol. Cell. Biol. 19 (1): 916–22. PMC 83949. PMID 9858615. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=83949. 
• Sexl V, Diehl JA, Sherr CJ, et al. (1999). "A rate limiting function of cdc25A for S phase entry inversely correlates with tyrosine dephosphorylation of Cdk2". Oncogene 18 (3): 573–82. doi:10.1038/sj.onc.1202362. PMID 9989807. 
• Mochizuki T, Kitanaka C, Noguchi K, et al. (1999). "Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway". J. Biol. Chem. 274 (26): 18659–66. doi:10.1074/jbc.274.26.18659. PMID 10373478. 
• Xia K, Lee RS, Narsimhan RP, et al. (1999). "Tyrosine Phosphorylation of the Proto-Oncoprotein Raf-1 Is Regulated by Raf-1 Itself and the Phosphatase Cdc25A". Mol. Cell. Biol. 19 (7): 4819–24. PMC 84280. PMID 10373531. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84280. 
• Vigo E, Müller H, Prosperini E, et al. (1999). "CDC25A Phosphatase Is a Target of E2F and Is Required for Efficient E2F-Induced S Phase". Mol. Cell. Biol. 19 (9): 6379–95. PMC 84608. PMID 10454584. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84608.