Difference between revisions of "Phosphatase Subfamily CDC25"
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=== Catalytic activity and functions === | === Catalytic activity and functions === | ||
| − | Cdc25 dephosphorylates CDK kinases in many organisms, including yeasts, | + | Cdc25 dephosphorylates CDK kinases in many organisms, including yeasts, Drosophila and mammals, and so controls checkpoint progression of the cell cycle. CDC25 structures and functions have been reviewed in detail <cite>boutros06, rudolph07, boutros07</cite>. CDC25 removes inhibitory phosphates added by Wee1 from a threonine and a tyrosine in the G-loop of CDK1 and other CDKs, activating their cell cycle function. Duplicated CDC25s often have specific subfunctions: in Drosophila, string (stg) is involved in mitosis, and twine in meiosis, while in mammals, CDC25A is involved in the G1-S checkpoint (dephosphorylating CDK2, CDK4 and CDK6) <cite>Shen</cite>, and CDC25B and CDC25C are involved at G2-M. |
=== References === | === References === | ||
Revision as of 01:41, 23 August 2015
Phosphatase Classification: Fold CC3 (Rhondanese): Superfamily CC3 (Rhondanese): Family CDC25: Subfamily CDC25
Evolution
The CDC25 subfamily is found in a broad of eukaryotes, but absent from most if not all of plants. It has multiple copies in many species, including three in human, two in Drosophila and four in C. elegans, all from apparently independent duplications.
Domain
Human CDC25s have an N-terminal regulatory domain known as M-phase inducer phosphatase domain and a C-terminal phosphatase domain with a rhodanese fold. Both human CDC25s show alternative splicing of the regulatory domain. The N-terminal regulatory domain is classified as tetrapod-specific in Pfam, but has clearly conserved homology with CDC25 genes across the metazoa.
Catalytic activity and functions
Cdc25 dephosphorylates CDK kinases in many organisms, including yeasts, Drosophila and mammals, and so controls checkpoint progression of the cell cycle. CDC25 structures and functions have been reviewed in detail [1, 2, 3]. CDC25 removes inhibitory phosphates added by Wee1 from a threonine and a tyrosine in the G-loop of CDK1 and other CDKs, activating their cell cycle function. Duplicated CDC25s often have specific subfunctions: in Drosophila, string (stg) is involved in mitosis, and twine in meiosis, while in mammals, CDC25A is involved in the G1-S checkpoint (dephosphorylating CDK2, CDK4 and CDK6) [4], and CDC25B and CDC25C are involved at G2-M.
References
- Boutros R, Dozier C, and Ducommun B. The when and wheres of CDC25 phosphatases. Curr Opin Cell Biol. 2006 Apr;18(2):185-91. DOI:10.1016/j.ceb.2006.02.003 |
- Rudolph J. Cdc25 phosphatases: structure, specificity, and mechanism. Biochemistry. 2007 Mar 27;46(12):3595-604. DOI:10.1021/bi700026j |
- 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 |
