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Gene Review

CDC25C  -  cell division cycle 25C

Homo sapiens

Synonyms: CDC25, Dual specificity phosphatase Cdc25C, M-phase inducer phosphatase 3, PPP1R60
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Disease relevance of CDC25C

  • CDC25C protein is up-regulated in prostate cancer in comparison with normal prostate tissue and is present almost exclusively in its active dephosphorylated form [1].
  • Our objective was to evaluate the expression of the three cell cycle-related phosphatases CDC25A, CDC25B and CDC25C in patients with ovarian cancer [2].
  • G2 arrest induced by nitrogen mustard in human lymphoma CA46 cells is associated with a failure to activate hyperphosphorylated cdc2/cyclin B1 complexes [3].
  • Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cells [4].

High impact information on CDC25C

  • Here we show that the catalytic activity of human cdc25-C phosphatase is also activated directly by phosphorylation in mitotic cells [5].
  • Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis [5].
  • Cells arrested in G2 phase following nitrogen mustard treatment or cells arrested in S phase with aphidicolin failed to dephosphorylate and activate cdc2, and this correlated with failure to convert cdc25C into the most active hyperphosphorylated species [3].
  • Temozolomide-treated cells induced to overexpress Akt, however, exhibited significantly less drug-induced Cdc25C/Cdc2 inactivation and less G2 arrest [6].
  • Our results show that whereas CDC25C is expressed at a low level with no relevant differences between neoplastic tissue and normal mucosa, CDC25A and CDC25B are overexpressed in a large fraction of tumors [7].

Chemical compound and disease context of CDC25C


Biological context of CDC25C


Anatomical context of CDC25C

  • To determine whether CDC25C activity is altered in prostate cancer, we have examined the expression of CDC25C and an alternatively spliced variant in human prostate cancer samples and cell lines [1].
  • The bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase-dependent CDK1 dephosphorylation and activation [14].
  • A Polo-like kinase 1 (Plk1) appears involved in an autocatalytic loop between CDC25C phosphatase and M phase promoting factor (MPF) in Xenopus oocytes and leads to activation of MPF that is required for germinal vesicle breakdown (GVBD) [15].
  • Radiation with 1 Gy prevents the activation of the mitotic inducers mitosis-promoting factor (MPF) and cdc25-C in HeLa cells [16].
  • We recently demonstrated that cdc2 expression is associated with the biological aggressiveness of malignant lymphoma of the thyroid [17].

Associations of CDC25C with chemical compounds


Enzymatic interactions of CDC25C

  • For its activation at the G2/M border, p34cdc2 needs to be associated with cyclin B and additionally dephosphorylated at Tyr-15 by the specific phosphatase cdc25-C [4].
  • The basic mechanism of this assay is to observe the phosphorylated levels of a fragment of CDC25C containing the site that can be phosphorylated by CHK1 in vitro [22].

Regulatory relationships of CDC25C


Other interactions of CDC25C

  • Western blot was employed to measure nuclear protein abundance of CDC25A, CDC25B, CDC25C, total p34cdc2, p34cdc2, (Thr 161) or p34cdc2 (Thr 14, Tyr 15) [18].
  • Based on this analysis of Ki67 expression, some but not all of this increase in CDC25C and its alternatively spliced variants is correlated with increased proliferation in prostate cancer [1].
  • However, the relationship between HPV typing and ATM, chk2, CDC25C and cyclinB1 expression was not significant [27].
  • This p14(ARF)-induced G(2) arrest was correlated with inhibition of CDC2 activity, inactivation of CDC25C phosphatase and induction of the CDK inhibitor p21(WAFI) [28].
  • Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12, respectively [29].

Analytical, diagnostic and therapeutic context of CDC25C


  1. Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer. Ozen, M., Ittmann, M. Clin. Cancer Res. (2005) [Pubmed]
  2. Cell cycle-related phosphatases CDC25A and B expression correlates with survival in ovarian cancer patients. Broggini, M., Buraggi, G., Brenna, A., Riva, L., Codegoni, A.M., Torri, V., Lissoni, A.A., Mangioni, C., D'Incalci, M. Anticancer Res. (2000) [Pubmed]
  3. Role of the cdc25C phosphatase in G2 arrest induced by nitrogen mustard. O'Connor, P.M., Ferris, D.K., Hoffmann, I., Jackman, J., Draetta, G., Kohn, K.W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. Clostridium botulinum C2 toxin delays entry into mitosis and activation of p34cdc2 kinase and cdc25-C phosphatase in HeLa cells. Barth, H., Klingler, M., Aktories, K., Kinzel, V. Infect. Immun. (1999) [Pubmed]
  5. Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis. Hoffmann, I., Clarke, P.R., Marcote, M.J., Karsenti, E., Draetta, G. EMBO J. (1993) [Pubmed]
  6. Akt activation suppresses Chk2-mediated, methylating agent-induced G2 arrest and protects from temozolomide-induced mitotic catastrophe and cellular senescence. Hirose, Y., Katayama, M., Mirzoeva, O.K., Berger, M.S., Pieper, R.O. Cancer Res. (2005) [Pubmed]
  7. Overexpression of CDC25A and CDC25B in head and neck cancers. Gasparotto, D., Maestro, R., Piccinin, S., Vukosavljevic, T., Barzan, L., Sulfaro, S., Boiocchi, M. Cancer Res. (1997) [Pubmed]
  8. Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells. Xiao, D., Johnson, C.S., Trump, D.L., Singh, S.V. Mol. Cancer Ther. (2004) [Pubmed]
  9. Caffeine induces TP53-independent G(1)-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner. Qi, W., Qiao, D., Martinez, J.D. Radiat. Res. (2002) [Pubmed]
  10. Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C. Wegener, S., Hampe, W., Herrmann, D., Schaller, H.C. Eur. J. Cell Biol. (2000) [Pubmed]
  11. Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation. Davezac, N., Baldin, V., Blot, J., Ducommun, B., Tassan, J.P. Oncogene (2002) [Pubmed]
  12. Fisetin inhibits the activities of cyclin-dependent kinases leading to cell cycle arrest in HT-29 human colon cancer cells. Lu, X., Jung, J., Cho, H.J., Lim, d.o. .Y., Lee, H.S., Chun, H.S., Kwon, D.Y., Park, J.H. J. Nutr. (2005) [Pubmed]
  13. Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15.3-11p15.1 by fluorescence in situ hybridization. Taviaux, S.A., Demaille, J.G. Genomics (1993) [Pubmed]
  14. Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase. Alby, F., Mazars, R., de Rycke, J., Guillou, E., Baldin, V., Darbon, J.M., Ducommun, B. FEBS Lett. (2001) [Pubmed]
  15. Timing of Plk1 and MPF activation during porcine oocyte maturation. Anger, M., Klima, J., Kubelka, M., Prochazka, R., Motlik, J., Schultz, R.M. Mol. Reprod. Dev. (2004) [Pubmed]
  16. Radiation with 1 Gy prevents the activation of the mitotic inducers mitosis-promoting factor (MPF) and cdc25-C in HeLa cells. Barth, H., Hoffmann, I., Kinzel, V. Cancer Res. (1996) [Pubmed]
  17. Polo-like kinase 1 (PLK1) expression is associated with cell proliferative activity and cdc2 expression in malignant lymphoma of the thyroid. Ito, Y., Yoshida, H., Matsuzuka, F., Matsuura, N., Nakamura, Y., Nakamine, H., Kakudo, K., Kuma, K., Miyauchi, A. Anticancer Res. (2004) [Pubmed]
  18. Failure to inactivate CDK activity is responsible for the enhanced apoptotic response in U937 cells mediated by silencing ATM gene. Deng, J., Zhou, J., Meng, F., Li, D., Sun, H. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. (2002) [Pubmed]
  19. Synthesis and biological evaluation of novel heterocyclic quinones as inhibitors of the dual specificity protein phosphatase CDC25C. Lavergne, O., Fernandes, A.C., Bréhu, L., Sidhu, A., Brézak, M.C., Prévost, G., Ducommun, B., Contour-Galcera, M.O. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  20. Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. Singh, S.V., Herman-Antosiewicz, A., Singh, A.V., Lew, K.L., Srivastava, S.K., Kamath, R., Brown, K.D., Zhang, L., Baskaran, R. J. Biol. Chem. (2004) [Pubmed]
  21. Benzyl isothiocyanate-induced DNA damage causes g2/m cell cycle arrest and apoptosis in human pancreatic cancer cells. Zhang, R., Loganathan, S., Humphreys, I., Srivastava, S.K. J. Nutr. (2006) [Pubmed]
  22. CHK1 kinase activity assay. Wang, Y., Wang, H. Methods Mol. Biol. (2004) [Pubmed]
  23. Specific interaction between 14-3-3 isoforms and the human CDC25B phosphatase. Mils, V., Baldin, V., Goubin, F., Pinta, I., Papin, C., Waye, M., Eychene, A., Ducommun, B. Oncogene (2000) [Pubmed]
  24. Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains. Ng, C.P., Lee, H.C., Ho, C.W., Arooz, T., Siu, W.Y., Lau, A., Poon, R.Y. J. Biol. Chem. (2004) [Pubmed]
  25. CDK1-cyclin B1 mediates the inhibition of proliferation induced by omega-3 fatty acids in MDA-MB-231 breast cancer cells. Barascu, A., Besson, P., Le Floch, O., Bougnoux, P., Jourdan, M.L. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  26. Human p53 restores DNA synthesis control in fission yeast. Bureik, M., Jungbluth, A., Drescher, R., Wagner, P. Biol. Chem. (1997) [Pubmed]
  27. Relationship between HPV typing and the status of G2 cell cycle regulators in cervical neoplasia. Hashiguchi, Y., Tsuda, H., Nishimura, S., Inoue, T., Kawamura, N., Yamamoto, K. Oncol. Rep. (2004) [Pubmed]
  28. p14ARF induces G2 arrest and apoptosis independently of p53 leading to regression of tumours established in nude mice. Eymin, B., Leduc, C., Coll, J.L., Brambilla, E., Gazzeri, S. Oncogene (2003) [Pubmed]
  29. Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12, respectively. Sartor, H., Ehlert, F., Grzeschik, K.H., Müller, R., Adolph, S. Genomics (1992) [Pubmed]
  30. Reduction of 14-3-3 proteins correlates with increased sensitivity to killing of human lung cancer cells by ionizing radiation. Qi, W., Martinez, J.D. Radiat. Res. (2003) [Pubmed]
  31. Characterization of the interactions between human cdc25C, cdks, cyclins and cdk-cyclin complexes. Morris, M.C., Divita, G. J. Mol. Biol. (1999) [Pubmed]
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