Phosphatase Family CDC25
Phosphatase Classification: Superfamily Cys-based II: Family CDC25
Function
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 [1].
CDC25 has a phosphatase domain belonging to the rhodanese fold in the C-terminus [2, 3], and a less-conserved N-terminal regulatory region [4], which can be phosphorylated and ubiquitinated.
Evolution
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.
Plants contain a phosphatase called Arc2. It is a dubious CDC25. While it shows the phosphatase activity towards CDKs in vitro, its overexpression or knock-out have no obvious cell cycle phenotype [5]. Arc2 can also be found in fungi, Amoebozoans, Heterokonts, Excavates. In several cases, Arc2 and CDC25 are mutually exclusive: in algae, Arc2 is in Chlamydomonas but not Ostreococcus, and Arc2 is absent from holozoans.
Based upon their phylogenetic profiles, the possible history is the basal eukaryotes have both of the two genes, and got lost in some branches. While some organisms have both of the genes, both are lost in Alveolates. It is interesting taking account of its function in cell cycle regulation and checkpoint of DNA damage.
References
- 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 |
- 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 |
- Boudolf V, Inzé D, and De Veylder L. What if higher plants lack a CDC25 phosphatase?. Trends Plant Sci. 2006 Oct;11(10):474-9. DOI:10.1016/j.tplants.2006.08.009 |
