Cdc25

Cdc25 is a dual-specificity phosphatase first isolated from the yeast Schizosaccharomyces pombe as a cell cycle defective mutant. As with other cell cycle proteins such as Cdc2 and Cdc4, the "cdc" in its name refers to "cell division cycle". Dual-specificity phosphatases are considered a sub-class of protein tyrosine phosphatases. By removing inhibitory phosphate residues from target Cyclin-Dependent Kinases (Cdks)^[1], Cdc25 proteins control entry into and progression through various phases of the cell cycle, including mitosis and S ("Synthesis") phase.

Evolution and Species Distribution

Cdc25 enzymes are well conserved through evolution, and have been isolated from fungi such as nematode Caenorhabditis elegans, which has four distinct Cdc25 genes (Cdc-25.1 to Cdc-25.4)^[6].

Knockout Models

Although the highly conserved nature of the Cdc25s implies an important role in cell physiology, Cdc25B and Cdc25C knockout mice (both single and double mutants) are viable and display no major alterations in their cell cycles^[7], suggesting some functional compensation either via other Cdk regulatory enzymes (such as Wee1 and Mik1) or from the activity of the third member of the family, Cdc25A. Hiroaki Kiyokawa's laboratory has shown that Cdc25A knockout mice are not viable.

Cdc25s in Human Disease

The Cdc25s, and in particular Cdc25A and Cdc25B, have been shown to be overexpressed in a number of cancers^[8]. The central role of Cdc25s in the cell cycle has garnered them considerable attention from the pharmaceutical industry as potential targets for novel chemotherapeutic (anti-cancer) agents. To date, no clinically-viable compounds targeting these enzymes have been described.

References

^ Cdc2 Dephosphorylation and Activation
^ First human Cdc25 isolated
^ Arabidopsis Cdc25
^ String cloning
^ Twine meiosis
^ Nematode Cdc25s
^ Cdc25B/C Knockouts
^ Cdc25 in Cancer

Genes

CDC25A
CDC25B
CDC25C