Phosphtase Subfamily CDC25
Phosphatase Classification: Superfamily Cys-based II (Rhondanese): Family CDC25: Subamily CDC25
CDC25 composes of a catalytic domain on the C-terminus [1, 2], and a less-conserved N-terminal regulatory region [3], which can be phosphorylated and ubiquitinated. CDC25 activates cyclin-dependent kinases (CDKs) by dephosphorylating two sites within their ATP binding loop. CDKs regulate key transitions between cell cycle phases, and are key components of the checkpoint pathways involved in DNA damage. Thus, it is not suppressing to find it overexpressed in many human cancers [4].
CDC25s can be found through the unikonts (fungi, animal, amoebazoans), and in a few other eukaryotes. Within plants, they are only found in the alga Ostreococcus, but not Chalmydomonas, and are absent from land plants. In excavates, they are found in Trichomonas, but not Giardia, Leishmania, or Trypanosomes.
References
- Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, and Saper MA. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998 May 15;93(4):617-25. DOI:10.1016/s0092-8674(00)81190-3 |
- Reynolds RA, Yem AW, Wolfe CL, Deibel MR Jr, Chidester CG, and Watenpaugh KD. Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol. 1999 Oct 29;293(3):559-68. DOI:10.1006/jmbi.1999.3168 |
- Forrest A and Gabrielli B. Cdc25B activity is regulated by 14-3-3. Oncogene. 2001 Jul 19;20(32):4393-401. DOI:10.1038/sj.onc.1204574 |
- Boutros R, Lobjois V, and Ducommun B. CDC25 phosphatases in cancer cells: key players? Good targets?. Nat Rev Cancer. 2007 Jul;7(7):495-507. DOI:10.1038/nrc2169 |
