Difference between revisions of "Phosphtase Subfamily CDC25"

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__NOTOC__
 
__NOTOC__
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_Cys-based_II|Superfamily Cys-based II]]: [[Phosphatase_Family_CDC25|Family CDC25]]: [[Subfamily_CDC25|Subamily CDC25]]
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_CC3|Superfamily CC3 (Rhodanese)]]: [[Phosphatase_Family_CDC25|Family CDC25]]: [[Phosphatse_Subfamily_CDC25|Subfamily CDC25]]
  
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CDC25 activates cyclin-dependent kinases ([http://kinase.com/wiki/index.php/Kinase_Family_CDK 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 <cite>Boutros07</cite>.
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CDC25 subfamily has three member genes in human, '''[[Gene_CDC25A|CDC25A]]''', '''[[Gene_CDC25B|CDC25B]]''', '''[[Gene_CDC25C|CDC25C]]'''. They contain a catalytic domain on the C-terminus <cite>fauman98 reynolds99</cite>, and a less-conserved N-terminal regulatory region <cite>forrest01</cite>, which can be phosphorylated and ubiquitinated. CDC25 activates cyclin-dependent kinases ([http://kinase.com/wiki/index.php/Kinase_Family_CDK 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 <cite>Boutros07</cite>.
  
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CDC25 has a phosphatase domain belonging to the rhodanese fold in the C-terminus <cite>fauman98 reynolds99</cite>, and a less-conserved N-terminal regulatory region <cite>forrest01</cite>, which can be phosphorylated and ubiquitinated.
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CDC25 is found in most animals, but is absent from land plants and green alga ''Chalmydomonas''.  In excavates, they are found in ''Trichomonas'', but not ''Giardia'', ''Leishmania'', or ''Trypanosomes''.
  
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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.
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==== References ====
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Plants contain a dubious phosphatase called [[Subfamily_Acr2|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 <cite>Boudolf06</cite>. 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.
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== References ==
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<biblio>
 
<biblio>
 
#forrest01 pmid=11466620
 
#forrest01 pmid=11466620
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#fauman98 pmid=9604936
 
#fauman98 pmid=9604936
 
#Boutros07 pmid=17568790
 
#Boutros07 pmid=17568790
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#Boudolf06 pmid=16949857
 
 
</biblio>
 
</biblio>

Latest revision as of 01:48, 23 August 2015

Phosphatase Classification: Superfamily CC3 (Rhodanese): Family CDC25: Subfamily CDC25

CDC25 subfamily has three member genes in human, CDC25A, CDC25B, CDC25C. They contain a catalytic domain on the C-terminus [1, 2], and a less-conserved N-terminal regulatory region [3], which can be phosphorylated and ubiquitinated. 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 [4].

CDC25 is found in most animals, but is absent from land plants and green alga Chalmydomonas. In excavates, they are found in Trichomonas, but not Giardia, Leishmania, or Trypanosomes.

References

  1. Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, and Saper MA. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998 May 15;93(4):617-25. DOI:10.1016/s0092-8674(00)81190-3 | PubMed ID:9604936 | HubMed [fauman98]
  2. Reynolds RA, Yem AW, Wolfe CL, Deibel MR Jr, Chidester CG, and Watenpaugh KD. Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol. 1999 Oct 29;293(3):559-68. DOI:10.1006/jmbi.1999.3168 | PubMed ID:10543950 | HubMed [reynolds99]
  3. Forrest A and Gabrielli B. Cdc25B activity is regulated by 14-3-3. Oncogene. 2001 Jul 19;20(32):4393-401. DOI:10.1038/sj.onc.1204574 | PubMed ID:11466620 | HubMed [forrest01]
  4. 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 | PubMed ID:17568790 | HubMed [Boutros07]
All Medline abstracts: PubMed | HubMed
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