Cdc25 3610203 218626263 2008-06-11T13:48:54Z 83.81.184.45 i changed mik1 in myt1 '''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 "'''c'''ell '''d'''ivision '''c'''ycle". Dual-specificity phosphatases are considered a sub-class of [[protein tyrosine phosphatases]]. By removing inhibitory phosphate residues from target [[Cyclin-Dependent Kinase]]s (Cdks)<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1828290 Cdc2 Dephosphorylation and Activation]</ref>, Cdc25 proteins control entry into and progression through various phases of the [[cell cycle]], including [[mitosis]] and S ("'''S'''ynthesis") phase. ==Evolution and Species Distribution== Cdc25 enzymes are well conserved through evolution, and have been isolated from [[fungi]] such as [[yeast]]s as well as all [[metazoan]]s examined to date, including humans<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2195549 First human Cdc25 isolated]</ref>. The exception among eukaryotes may be [[plant]]s, as the purported plant Cdc25s have characteristics, (such as the use of cations for catalysis), that are more akin to [[serine/threonine phosphatase]]s than [[dual-specificity phosphatase]]s, raising doubts as to their authenticity as Cdc25 phosphatases<ref>[http://www.pnas.org/cgi/content/full/101/36/13380 Arabidopsis Cdc25]</ref>. 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]]<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2702688 String cloning]</ref> and [[meiosis]]<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1606618 Twine meiosis]</ref>, respectively. Most other [[model organisms]] examined have three Cdc25s, designated Cdc25A, Cdc25B, and [[CDC25C|Cdc25C]]. An exception is the [[nematode]] [[Caenorhabditis elegans]], which has four distinct Cdc25 genes (Cdc-25.1 to Cdc-25.4)<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9651482 Nematode Cdc25s] </ref>. ==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<ref>[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15767688 Cdc25B/C Knockouts]</ref>, 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 [[cancer]]s<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15324805 Cdc25 in Cancer]</ref>. 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== <div class="references-small"> <references/> </div> ==Genes== * {{Gene|CDC25A}} * {{Gene|CDC25B}} * {{Gene|CDC25C}} ==See also== *[[Cyclin]] *[[Cell Cycle]] *[[Cyclin-dependent kinase]] *[[Wee1]] {{Protein tyrosine phosphatases}} {{Cell cycle proteins}} [[Category:Enzymes]] [[Category:Cell cycle]]