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) [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1828290 Cdc2 Dephosphorylation and Activation] ] , 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 yeasts as well as all metazoans examined to date, including humans [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2195549 First human Cdc25 isolated] ] . The exception among eukaryotes may be plants, as the purported plant Cdc25s have characteristics, (such as the use of cations for catalysis), that are more akin to serine/threonine phosphatases than dual-specificity phosphatases, raising doubts as to their authenticity as Cdc25 phosphatases [ [http://www.pnas.org/cgi/content/full/101/36/13380 Arabidopsis Cdc25] ] . The Cdc25 family appears to have expanded in relation to the complexity of the cell-cycle and life-cycle of higher animals. Yeasts have a single Cdc25 (as well as a distantly related enzyme known as Itsy-bitsy phosphatase 1, or Ibp1). "Drosophila melanogaster" has two Cdc25s, known as "string" and "twine", which control mitosis [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2702688 String cloning] ] and meiosis [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1606618 Twine meiosis] ] , respectively. Most other model organisms examined have three Cdc25s, designated Cdc25A, Cdc25B, and Cdc25C. An exception is the nematode Caenorhabditis elegans, which has four distinct Cdc25 genes (Cdc-25.1 to Cdc-25.4) [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9651482 Nematode Cdc25s] ] .

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 [ [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15767688 Cdc25B/C Knockouts] ] , suggesting some functional compensation either via other Cdk regulatory enzymes (such as Wee1 and Myt1) 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 [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15324805 Cdc25 in Cancer] ] . 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

Genes

*
*
*

ee also

*Cyclin
*Cell Cycle
*Cyclin-dependent kinase
*Wee1