Phosphatase Family CDC25

Phosphatase Classification: Superfamily Cys-based II: Family CDC25

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.

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 dubious phosphatase called Acr2. 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]. Acr2 can also be found in fungi, Amoebozoans, Heterokonts, Excavates. In several cases, Acr2 and CDC25 are mutually exclusive: in algae, Acr2 is in Chlamydomonas but not Ostreococcus, and Acr2 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

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