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.
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 two (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 canceredit
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.[5]
^Galaktionov K, Jessus C, Beach D (May 1995). "Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation" (PDF). Genes Dev. 9 (9): 1046–58. doi:10.1101/gad.9.9.1046. PMID 7744247.
^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.
^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. doi:10.4161/cc.2.5.482. PMID 12963847.
^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.
^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. Bibcode:2002PNAS...9914795Z. doi:10.1073/pnas.182557299. PMC137498. PMID 12399544.
^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. PMC2443656. PMID 18480045.
^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. doi:10.1128/mcb.19.2.1460. PMC116074. PMID 9891079.
^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.
^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.
^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.
^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. Bibcode:1995PNAS...92.7892C. doi:10.1073/pnas.92.17.7892. PMC41252. PMID 7644510.
External linksedit
Human CDC25A genome location and CDC25A gene details page in the UCSC Genome Browser.
Further readingedit
Parsons R (1998). "Phosphatases and tumorigenesis". Current Opinion in Oncology. 10 (1): 88–91. doi:10.1097/00001622-199801000-00014. PMID 9466490. S2CID 33899887.
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. S2CID 19673633.
Nilsson I, Hoffmann I (2000). "Cell cycle regulation by the Cdc25 phosphatase family". Progress in Cell Cycle Research. Vol. 4. pp. 107–14. doi:10.1007/978-1-4615-4253-7_10. ISBN978-1-4613-6909-7. 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. S2CID 9659637.
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. Bibcode:1995PNAS...92.7892C. doi:10.1073/pnas.92.17.7892. PMC41252. PMID 7644510.
Galaktionov K, Lee AK, Eckstein J, Draetta G, Meckler J, Loda M, Beach D (1995). "CDC25 phosphatases as potential human oncogenes". Science. 269 (5230): 1575–7. Bibcode:1995Sci...269.1575G. 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" (PDF). 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, Resnitzky D, Hoffman I, Reed SI, Kimchi A (1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Mol. Cell. Biol. 16 (7): 3934–44. doi:10.1128/mcb.16.7.3934. PMC231390. PMID 8668211.
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, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, Saper MA (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. S2CID 5762201.
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. PMC1170797. PMID 9707427.
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. doi:10.1128/mcb.19.1.916. PMC83949. PMID 9858615.
Sexl V, Diehl JA, Sherr CJ, Ashmun R, Beach D, Roussel MF (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, Muramatsu T, Asai A, Kuchino Y (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, Mukhopadhyay NK, Neel BG, Roberts TM (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. doi:10.1128/mcb.19.7.4819. PMC84280. PMID 10373531.
Vigo E, Müller H, Prosperini E, Hateboer G, Cartwright P, Moroni MC, Helin K (1999). "CDC25A Phosphatase Is a Target of E2F and Is Required for Efficient E2F-Induced S Phase". Mol. Cell. Biol. 19 (9): 6379–95. doi:10.1128/mcb.19.9.6379. PMC84608. PMID 10454584.
April 12, 2024
cdc25a, phase, inducer, phosphatase, also, known, dual, specificity, phosphatase, cdc25a, protein, that, humans, encoded, cell, division, cycle, homolog, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes1c25identifiersaliases, cell, divisio. 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 CDC25AAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1C25IdentifiersAliasesCDC25A CDC25A2 cell division cycle 25AExternal IDsOMIM 116947 MGI 103198 HomoloGene 1355 GeneCards CDC25AGene location Human Chr Chromosome 3 human 1 Band3p21 31Start48 157 146 bp 1 End48 188 417 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 F2 9 59 81 cMStart109 704 647 bp 2 End109 722 963 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insecondary oocyteembryospermspongy boneganglionic eminencebone marrowbone marrow cellstesticlepalpebral conjunctivaretinal pigment epitheliumTop expressed inotic placodesacculeprimitive streaksomiteyolk sacmaxillary prominenceabdominal wallepithelium of stomachduodenummedial ganglionic eminenceMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein binding protein tyrosine phosphatase activity hydrolase activity protein kinase binding phosphoprotein phosphatase activity chaperone bindingCellular componentcytoplasm cytosol intracellular anatomical structure nucleoplasm nucleusBiological processregulation of cyclin dependent protein serine threonine kinase activity cellular response to UV protein dephosphorylation regulation of cell cycle cell division G2 M transition of mitotic cell cycle cell cycle response to radiation peptidyl tyrosine dephosphorylation cell population proliferation protein deubiquitination positive regulation of cell cycle G2 M phase transition G1 S transition of mitotic cell cycle positive regulation of G2 M transition of mitotic cell cycle positive regulation of mitotic cell cycle positive regulation of G2 MI transition of meiotic cell cycleSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez99312530EnsemblENSG00000164045ENSMUSG00000032477UniProtP30304P48964RefSeq mRNA NM 001789NM 201567NM 007658RefSeq protein NP 001780NP 963861NP 031684Location UCSC Chr 3 48 16 48 19 MbChr 9 109 7 109 72 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Involvement in cancer 3 Interactions 4 References 5 External links 6 Further readingFunction editCDC25A 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 two 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 editCDC25A 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 amp 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 5 Interactions editCDC25A has been shown to interact with ASK1 6 C Raf 7 8 CHEK1 9 10 11 12 CCNE1 13 14 EGFR 15 PIM1 16 and YWHAB 17 References edit a b c GRCh38 Ensembl release 89 ENSG00000164045 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000032477 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene CDC25A cell division cycle 25 homolog A S pombe 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 Galaktionov K Jessus C Beach D May 1995 Raf1 interaction with Cdc25 phosphatase ties mitogenic signal transduction to cell cycle activation PDF Genes Dev 9 9 1046 58 doi 10 1101 gad 9 9 1046 PMID 7744247 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 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 doi 10 4161 cc 2 5 482 PMID 12963847 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 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 Bibcode 2002PNAS 9914795Z doi 10 1073 pnas 182557299 PMC 137498 PMID 12399544 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 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 doi 10 1128 mcb 19 2 1460 PMC 116074 PMID 9891079 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 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 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 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 Bibcode 1995PNAS 92 7892C doi 10 1073 pnas 92 17 7892 PMC 41252 PMID 7644510 External links editHuman CDC25A genome location and CDC25A gene details page in the UCSC Genome Browser Further reading editParsons R 1998 Phosphatases and tumorigenesis Current Opinion in Oncology 10 1 88 91 doi 10 1097 00001622 199801000 00014 PMID 9466490 S2CID 33899887 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 S2CID 19673633 Nilsson I Hoffmann I 2000 Cell cycle regulation by the Cdc25 phosphatase family Progress in Cell Cycle Research Vol 4 pp 107 14 doi 10 1007 978 1 4615 4253 7 10 ISBN 978 1 4613 6909 7 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 S2CID 9659637 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 Bibcode 1995PNAS 92 7892C doi 10 1073 pnas 92 17 7892 PMC 41252 PMID 7644510 Galaktionov K Lee AK Eckstein J Draetta G Meckler J Loda M Beach D 1995 CDC25 phosphatases as potential human oncogenes Science 269 5230 1575 7 Bibcode 1995Sci 269 1575G 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 PDF 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 Resnitzky D Hoffman I Reed SI Kimchi A 1996 Alpha interferon suppresses the cyclin D3 and cdc25A genes leading to a reversible G0 like arrest Mol Cell Biol 16 7 3934 44 doi 10 1128 mcb 16 7 3934 PMC 231390 PMID 8668211 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 Rocque WJ Holmes W Montana VG Piwnica Worms H Rink MJ Saper MA 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 S2CID 5762201 Coqueret O Berube 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 Iavarone A Massague J 1999 E2F and Histone Deacetylase Mediate Transforming Growth Factor b Repression of cdc25A during Keratinocyte Cell Cycle Arrest Mol Cell Biol 19 1 916 22 doi 10 1128 mcb 19 1 916 PMC 83949 PMID 9858615 Sexl V Diehl JA Sherr CJ Ashmun R Beach D Roussel MF 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 Muramatsu T Asai A Kuchino Y 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 Mukhopadhyay NK Neel BG Roberts TM 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 doi 10 1128 mcb 19 7 4819 PMC 84280 PMID 10373531 Vigo E Muller H Prosperini E Hateboer G Cartwright P Moroni MC Helin K 1999 CDC25A Phosphatase Is a Target of E2F and Is Required for Efficient E2F Induced S Phase Mol Cell Biol 19 9 6379 95 doi 10 1128 mcb 19 9 6379 PMC 84608 PMID 10454584 Retrieved from https en wikipedia org w index php title CDC25A amp oldid 1191281472, wikipedia, wiki, book, books, library,
