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Gene Review

CDC25B  -  cell division cycle 25B

Homo sapiens

Synonyms: CDC25HU2, Dual specificity phosphatase Cdc25B, M-phase inducer phosphatase 2
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Disease relevance of CDC25B


High impact information on CDC25B

  • A dual-specificity phosphatase Cdc25B is an unstable protein and triggers p34(cdc2)/cyclin B activation in hamster BHK21 cells arrested with hydroxyurea [5].
  • Selectivity of this inhibitor is demonstrated: (a) by the reversion of the mitotic-inducing effect observed in HeLa cells upon CDC25B overexpression; and (b) by the partial reversion of cell cycle arrest in U2OS expressing CDC25 [6].
  • CDC25B phosphatase plays a key role in controlling G2-M progression by dephosphorylating two inhibitory residues of CDC2 and also has been suggested to have an oncogenic property [4].
  • Without radiation, CDC25B overexpression had little effect on cell cycle fractions or growth rate [4].
  • Overexpression of CDC25B overrides radiation-induced G2-M arrest and results in increased apoptosis in esophageal cancer cells [4].

Biological context of CDC25B


Anatomical context of CDC25B

  • Knockdown experiments by RNAi confirm that the centrosome phosphorylation of CDC25B on S353 depends on Aurora-A kinase [12].
  • CDC25A and CDC25B cooperate with Ha-ras or loss of Rb1 in the oncogenic transformation of rodent fibroblasts [13].
  • Reverse transcription-PCR assay indicated that CDC25B was overexpressed in tumor tissues relative to normal mucosa in 6 of 10 cases [14].
  • Multivariate analysis indicated that CDC25B was an independent prognostic marker (risk ratio for death, 3.7; P < 0.0001) even after controlling for various factors such as lymph node metastasis, tumor size, degree of differentiation, and depth of invasion [14].
  • The results of the clinical specimens showed that the Fra-1 gene was overexpressed in ESCC compared with normal esophageal epithelium in 53 of 61 cases (87%), Neogenin in 57 of 61 cases (93%), Id-1 in 57 of 61 cases (93%), and CDC25B in 48 of 61 cases (79%) [15].

Associations of CDC25B with chemical compounds

  • However, phosphorylation of CDC25B does not stimulate its phosphatase activity, and mutation of serine 146 had no effect on its catalytic activity [8].
  • In addition to these binding-site differences, we found that the binding of 14-3-3beta drove CDC25B to the cytoplasm and that mutation of serine-309 to alanine completely abolished the cytoplasmic localization of CDC25B [9].
  • In contrast, p34cdc2 in U937-ASPI3K maintained in an active state by dephosphorylation on threonine 14 (Thr 14) and tyrosine 15 (Tyr 15), which was associated with constant nuclear CDC25A, CDC25B and CDC25C protein abundance before and after irradiation [16].
  • In studying the subcellular localization of CDC25B, we found a functional NES at V52 to L65, the sequence of which is VTTLTQTMHDLAGL, where bold letters are leucine or hydrophobic amino acids frequently seen in an NES [17].
  • Treatment with leptomycin B, a potent inhibitor of CRM1/exportin1, disrupted the cytoplasmic localization of both Flag-tagged CDC25B and NES-fused GFP [17].

Enzymatic interactions of CDC25B


Regulatory relationships of CDC25B


Other interactions of CDC25B


Analytical, diagnostic and therapeutic context of CDC25B


  1. Overexpression of cyclin-dependent kinase-activating CDC25B phosphatase in human gastric carcinomas. Kudo, Y., Yasui, W., Ue, T., Yamamoto, S., Yokozaki, H., Nikai, H., Tahara, E. Jpn. J. Cancer Res. (1997) [Pubmed]
  2. Expression and functional significance of CDC25B in human pancreatic ductal adenocarcinoma. Guo, J., Kleeff, J., Li, J., Ding, J., Hammer, J., Zhao, Y., Giese, T., Korc, M., Büchler, M.W., Friess, H. Oncogene (2004) [Pubmed]
  3. 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]
  4. Overexpression of CDC25B overrides radiation-induced G2-M arrest and results in increased apoptosis in esophageal cancer cells. Miyata, H., Doki, Y., Yamamoto, H., Kishi, K., Takemoto, H., Fujiwara, Y., Yasuda, T., Yano, M., Inoue, M., Shiozaki, H., Weinstein, I.B., Monden, M. Cancer Res. (2001) [Pubmed]
  5. A dual-specificity phosphatase Cdc25B is an unstable protein and triggers p34(cdc2)/cyclin B activation in hamster BHK21 cells arrested with hydroxyurea. Nishijima, H., Nishitani, H., Seki, T., Nishimoto, T. J. Cell Biol. (1997) [Pubmed]
  6. A novel synthetic inhibitor of CDC25 phosphatases: BN82002. Brezak, M.C., Quaranta, M., Mondésert, O., Galcera, M.O., Lavergne, O., Alby, F., Cazales, M., Baldin, V., Thurieau, C., Harnett, J., Lanco, C., Kasprzyk, P.G., Prevost, G.P., Ducommun, B. Cancer Res. (2004) [Pubmed]
  7. Phosphorylation of human CDC25B phosphatase by CDK1-cyclin A triggers its proteasome-dependent degradation. Baldin, V., Cans, C., Knibiehler, M., Ducommun, B. J. Biol. Chem. (1997) [Pubmed]
  8. Nuclear localization of CDC25B1 and serine 146 integrity are required for induction of mitosis. Baldin, V., Pelpel, K., Cazales, M., Cans, C., Ducommun, B. J. Biol. Chem. (2002) [Pubmed]
  9. Binding of 14-3-3beta but not 14-3-3sigma controls the cytoplasmic localization of CDC25B: binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B. Uchida, S., Kuma, A., Ohtsubo, M., Shimura, M., Hirata, M., Nakagama, H., Matsunaga, T., Ishizaka, Y., Yamashita, K. J. Cell. Sci. (2004) [Pubmed]
  10. Chromosome mapping of human CDC25A and CDC25B phosphatases. Demetrick, D.J., Beach, D.H. Genomics (1993) [Pubmed]
  11. Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas. Xu, X., Yamamoto, H., Sakon, M., Yasui, M., Ngan, C.Y., Fukunaga, H., Morita, T., Ogawa, M., Nagano, H., Nakamori, S., Sekimoto, M., Matsuura, N., Monden, M. Clin. Cancer Res. (2003) [Pubmed]
  12. Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G2-M transition. Dutertre, S., Cazales, M., Quaranta, M., Froment, C., Trabut, V., Dozier, C., Mirey, G., Bouché, J.P., Theis-Febvre, N., Schmitt, E., Monsarrat, B., Prigent, C., Ducommun, B. J. Cell. Sci. (2004) [Pubmed]
  13. 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]
  14. Overexpression of CDC25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma. Takemasa, I., Yamamoto, H., Sekimoto, M., Ohue, M., Noura, S., Miyake, Y., Matsumoto, T., Aihara, T., Tomita, N., Tamaki, Y., Sakita, I., Kikkawa, N., Matsuura, N., Shiozaki, H., Monden, M. Cancer Res. (2000) [Pubmed]
  15. Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC. Hu, Y.C., Lam, K.Y., Law, S., Wong, J., Srivastava, G. Clin. Cancer Res. (2001) [Pubmed]
  16. 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]
  17. Nuclear export signal in CDC25B. Uchida, S., Ohtsubo, M., Shimura, M., Hirata, M., Nakagama, H., Matsunaga, T., Yoshida, M., Ishizaka, Y., Yamashita, K. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  18. CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage. Schmitt, E., Boutros, R., Froment, C., Monsarrat, B., Ducommun, B., Dozier, C. J. Cell. Sci. (2006) [Pubmed]
  19. 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]
  20. Study of the cytolethal distending toxin-induced cell cycle arrest in HeLa cells: involvement of the CDC25 phosphatase. Escalas, N., Davezac, N., De Rycke, J., Baldin, V., Mazars, R., Ducommun, B. Exp. Cell Res. (2000) [Pubmed]
  21. 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]
  22. Biochemical and clinical approaches in evaluating the prognosis of colon cancer. Talvinen, K., Tuikkala, J., Gr??nroos, J., Huhtinen, H., Kronqvist, P., Aittokallio, T., Nevalainen, O., Hiekkanen, H., Nevalainen, T., Sundstr??m, J. Anticancer Res. (2006) [Pubmed]
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