BACKGROUND Cdc25 is a dual specificity phosphatase with three isoforms in mammalian cells - Cdc25A, B and C. Cdc25 activates Cdk complexes that control progression through the cell cycle. Cdc25 is also involved in the DNA damage checkpoints. Regulation of Cdc25 occurs through a variety of mechanisms including phosphorylation, interaction with 14.3.3 proteins, subcellular localization and protein degradation.1 Cdc25B is phosphorylated and activated by aurora kinase A at the start of mitosis, and as mitosis progresses is then further phosphorylated in an auto-amplification loop, along with Cdc25C, by the CDK1/cyclin B complex. Cdc25C is also phosphorylated during mitosis by PLK1, leading to greater activity of the CDK1/cyclin B complex. Similarly, Cdc25A acts during the G1/S phase of the cell cycle in concert with the CDK2/cyclin E complex. Both Cdc25A and Cdc25B can be activated by the DNA damage checkpoint kinase, Chk1 and thereby inhibit mitosis.2
Cdc25C is highly conserved during evolution and it plays a key role in the regulation of cell division. It is a tyrosine phosphatase and directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis.3 It is also thought to suppress p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described.
REFERENCES
1. Turowski,P. et al: Mol. Biol. Cell 14: 2984-98, 2003
2. Zwicker, J. et al: EMBO J. 14:4514-22, 1995
3. Mitra, J. & Schultz, R.M.: J. Cell Sci. 109:2407-2415, 1996
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