CDC25A

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Cell division cycle 25A
Protein CDC25A PDB 1c25.png
PDB rendering based on 1c25.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CDC25A ; CDC25A2
External IDs OMIM116947 MGI103198 HomoloGene1355 ChEMBL: 3775 GeneCards: CDC25A Gene
EC number 3.1.3.48
RNA expression pattern
PBB GE CDC25A 204695 at tn.png
PBB GE CDC25A 204696 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 993 12530
Ensembl ENSG00000164045 ENSMUSG00000032477
UniProt P30304 P48964
RefSeq (mRNA) NM_001789 NM_007658
RefSeq (protein) NP_001780 NP_031684
Location (UCSC) Chr 3:
48.2 – 48.23 Mb
Chr 9:
109.88 – 109.89 Mb
PubMed search [1] [2]

M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a protein that in humans is encoded by the cell division cycle 25 homolog A (CDC25A) gene.

Function[edit]

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 ancestral Cdc25 gene (found e.g. in the fungus species S. pombe , designated Cdc25A, Cdc25B, and Cdc25C. In contrast, some invertebrates harbour 2 (e.g., the Drosophila proteins 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.

Involvement in cancer[edit]

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.[1]

Interactions[edit]

CDC25A has been shown to interact with:

References[edit]

  1. ^ "Entrez Gene: CDC25A cell division cycle 25 homolog A (S. pombe)". 
  2. ^ Zou X, Tsutsui T, Ray D, Blomquist JF, Ichijo H, Ucker DS, Kiyokawa H (Jul 2001). "The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1". Mol. Cell. Biol. 21 (14): 4818–28. doi:10.1128/MCB.21.14.4818-4828.2001. PMC 87174. PMID 11416155. 
  3. ^ Galaktionov K, Jessus C, Beach D (May 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. 
  4. ^ Huang TS, Shu CH, Yang WK, Whang-Peng J (Jul 1997). "Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis". Cancer Res. 57 (14): 2974–8. PMID 9230211. 
  5. ^ Goloudina A, Yamaguchi H, Chervyakova DB, Appella E, Fornace AJ, Bulavin DV (2003). "Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint". Cell Cycle 2 (5): 473–8. PMID 12963847. 
  6. ^ Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ (Sep 1997). "Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25". Science 277 (5331): 1497–501. doi:10.1126/science.277.5331.1497. PMID 9278511. 
  7. ^ Zhao H, Watkins JL, Piwnica-Worms H (Nov 2002). "Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints". Proc. Natl. Acad. Sci. U.S.A. 99 (23): 14795–800. doi:10.1073/pnas.182557299. PMC 137498. PMID 12399544. 
  8. ^ Jin J, Ang XL, Ye X, Livingstone M, Harper JW (Jul 2008). "Differential roles for checkpoint kinases in DNA damage-dependent degradation of the Cdc25A protein phosphatase". J. Biol. Chem. 283 (28): 19322–8. doi:10.1074/jbc.M802474200. PMC 2443656. PMID 18480045. 
  9. ^ Shanahan F, Seghezzi W, Parry D, Mahony D, Lees E (Feb 1999). "Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest". Mol. Cell. Biol. 19 (2): 1460–9. PMC 116074. PMID 9891079. 
  10. ^ Xu X, Burke SP (Mar 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. 
  11. ^ Wang Z, Wang M, Lazo JS, Carr BI (May 2002). "Identification of epidermal growth factor receptor as a target of Cdc25A protein phosphatase". J. Biol. Chem. 277 (22): 19470–5. doi:10.1074/jbc.M201097200. PMID 11912208. 
  12. ^ Mochizuki T, Kitanaka C, Noguchi K, Muramatsu T, Asai A, Kuchino Y (Jun 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. 
  13. ^ Conklin DS, Galaktionov K, Beach D (Aug 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. 

Further reading[edit]