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CDC25A  -  cell division cycle 25 homolog A (S. pombe)

Homo sapiens

 
 
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Disease relevance of CDC25A

 

High impact information on CDC25A

  • We found that Cdc25 A degradation during mitotic exit and in early G(1) is mediated by the anaphase-promoting complex or cyclosome (APC/C)(Cdh1) ligase, and that a KEN-box motif in the N-terminus of the protein is required for its targeted degradation [6].
  • Here we have investigated the regulation of Cdc25 A in the cell cycle [6].
  • DNA damage or DNA replication blocks induce phosphorylation of Cdc25 A and its subsequent degradation via the ubiquitin-proteasome pathway [6].
  • Consistent with this observation, TGF-beta-treated cells failed to induce p15(INK4b), down-regulate CDC25A, or increase levels of p21(CIP1), p27(KIP1), and p57(KIP2) [7].
  • Supporting a role for Cdc25A in estrogen action, antisense CDC25A oligonucleotides inhibited estrogen-induced Cdk2 activation and DNA synthesis [8].
 

Biological context of CDC25A

 

Anatomical context of CDC25A

  • The gastric carcinoma cell lines expressed CDC25A, B and C mRNA at various levels [11].
  • CDC25A phosphatase promotes cell cycle progression by activating G(1) cyclin-dependent kinases and has been postulated to be an oncogene because of its ability to cooperate with RAS to transform rodent fibroblasts [12].
  • 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 [13].
  • Over-expression of CDK2 and CDC25a was also associated with reduced overall survival; moreover, the CDK2 expression level was able to define a short-living cohort of patients with tumour-positive lymph nodes [5].
  • BOULE protein expression in men with complete spermatogenesis can be restricted to stages from leptotene up to stages of late spermatocytes, whereas CDC25A expression ranges from leptotene spermatocytes to elongating spermatids [14].
 

Associations of CDC25A with chemical compounds

  • The data showed that aloesin increased the levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells [15].
  • The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored CDC25A degradation [16].
  • The conditional expression of the CDC25A gene using a tetracycline repressor expression vector increased sensitivity toward ART [17].
  • Kinase assays revealed that the reduction of p34(CDC2) activity by resveratrol was mediated through the inhibition of CDK7 kinase activity, while CDC25A phosphatase activity was not affected [18].
  • The purified compound 1 displayed significant inhibitory activity towards CDC25A (IC(50): 3 microM) [19].
 

Regulatory relationships of CDC25A

 

Other interactions of CDC25A

 

Analytical, diagnostic and therapeutic context of CDC25A

References

  1. 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]
  2. G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Gao, N., Flynn, D.C., Zhang, Z., Zhong, X.S., Walker, V., Liu, K.J., Shi, X., Jiang, B.H. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  3. Expression of cell cycle regulators in human cutaneous malignant melanoma. Tang, L., Li, G., Tron, V.A., Trotter, M.J., Ho, V.C. Melanoma Res. (1999) [Pubmed]
  4. 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]
  5. Expression of cyclin-dependent kinases and CDC25a phosphatase is related with recurrences and survival in women with peri- and post-menopausal breast cancer. Bonin, S., Brunetti, D., Benedetti, E., Gorji, N., Stanta, G. Virchows Arch. (2006) [Pubmed]
  6. Dual mode of degradation of Cdc25 A phosphatase. Donzelli, M., Squatrito, M., Ganoth, D., Hershko, A., Pagano, M., Draetta, G.F. EMBO J. (2002) [Pubmed]
  7. Transforming growth factor beta targeted inactivation of cyclin E:cyclin-dependent kinase 2 (Cdk2) complexes by inhibition of Cdk2 activating kinase activity. Nagahara, H., Ezhevsky, S.A., Vocero-Akbani, A.M., Kaldis, P., Solomon, M.J., Dowdy, S.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. Multifaceted regulation of cell cycle progression by estrogen: regulation of Cdk inhibitors and Cdc25A independent of cyclin D1-Cdk4 function. Foster, J.S., Henley, D.C., Bukovsky, A., Seth, P., Wimalasena, J. Mol. Cell. Biol. (2001) [Pubmed]
  9. DNA damage during the spindle-assembly checkpoint degrades CDC25A, inhibits cyclin-CDC2 complexes, and reverses cells to interphase. Chow, J.P., Siu, W.Y., Fung, T.K., Chan, W.M., Lau, A., Arooz, T., Ng, C.P., Yamashita, K., Poon, R.Y. Mol. Biol. Cell (2003) [Pubmed]
  10. Regulation of the mammalian cell cycle: a model of the G1-to-S transition. Qu, Z., Weiss, J.N., MacLellan, W.R. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  11. 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]
  12. The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1. Zou, X., Tsutsui, T., Ray, D., Blomquist, J.F., Ichijo, H., Ucker, D.S., Kiyokawa, H. Mol. Cell. Biol. (2001) [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. Association of meiotic arrest with lack of BOULE protein expression in infertile men. Luetjens, C.M., Xu, E.Y., Rejo Pera, R.A., Kamischke, A., Nieschlag, E., Gromoll, J. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  15. Aloesin up-regulates cyclin E/CDK2 kinase activity via inducing the protein levels of cyclin E, CDK2, and CDC25A in SK-HEP-1 cells. Lee, K.Y., Park, J.H., Chung, M.H., Park, Y.I., Kim, K.W., Lee, Y.J., Lee, S.K. Biochem. Mol. Biol. Int. (1997) [Pubmed]
  16. Lack of PTEN sequesters CHK1 and initiates genetic instability. Puc, J., Keniry, M., Li, H.S., Pandita, T.K., Choudhury, A.D., Memeo, L., Mansukhani, M., Murty, V.V., Gaciong, Z., Meek, S.E., Piwnica-Worms, H., Hibshoosh, H., Parsons, R. Cancer Cell (2005) [Pubmed]
  17. Molecular modes of action of artesunate in tumor cell lines. Efferth, T., Sauerbrey, A., Olbrich, A., Gebhart, E., Rauch, P., Weber, H.O., Hengstler, J.G., Halatsch, M.E., Volm, M., Tew, K.D., Ross, D.D., Funk, J.O. Mol. Pharmacol. (2003) [Pubmed]
  18. Resveratrol-induced G2 arrest through the inhibition of CDK7 and p34CDC2 kinases in colon carcinoma HT29 cells. Liang, Y.C., Tsai, S.H., Chen, L., Lin-Shiau, S.Y., Lin, J.K. Biochem. Pharmacol. (2003) [Pubmed]
  19. Coscinosulfate, a CDC25 phosphatase inhibitor from the sponge Coscinoderma mathewsi. Loukaci, A., Le Saout, I., Samadi, M., Leclerc, S., Damiens, E., Meijer, L., Debitus, C., Guyot, M. Bioorg. Med. Chem. (2001) [Pubmed]
  20. A fission yeast strain expressing human CDC25A phosphatase: a tool for selectivity studies of pharmacological inhibitors of CDC25. Mondesert, O., Lemaire, M., Brezak, M.C., Galera-Contour, M.O., Prevost, G., Ducommun, B., Bugler, B. Curr. Genet. (2004) [Pubmed]
  21. The Chk1/Cdc25A pathway as activators of the cell cycle in neuronal death induced by camptothecin. Zhang, Y., Qu, D., Morris, E.J., O'Hare, M.J., Callaghan, S.M., Slack, R.S., Geller, H.M., Park, D.S. J. Neurosci. (2006) [Pubmed]
  22. Chromosome mapping of human CDC25A and CDC25B phosphatases. Demetrick, D.J., Beach, D.H. Genomics (1993) [Pubmed]
  23. 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]
  24. Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals. Jekimovs, C.R., Chen, X., Arnold, J., Gatei, M., Richard, D.J., Spurdle, A.B., Khanna, K.K., Chenevix-Trench, G. Br. J. Cancer (2005) [Pubmed]
  25. Anomalies of the TGF-beta postreceptor signaling pathway in ovarian cancer cell lines. Hu, W., Wu, W., Nash, M.A., Freedman, R.S., Kavanagh, J.J., Verschraegen, C.F. Anticancer Res. (2000) [Pubmed]
 
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