Contents 1 Function in activating Cdk1 2 Structure 3 Evolution and species distribution 4 Knockout models 5 In human disease 6 See also 7 References 8 External links 8.1 Genes


Function in activating Cdk1[edit] Cdc25 activates cyclin dependent kinases by removing phosphate from residues in the Cdk active site. Also, the phosphorylation of M-Cdk (a complex of Cdk1 and cyclin B) activates Cdc25. Together with Wee1, M-Cdk activation is switch-like. The switch-like behavior forces entry into mitosis to be quick and irreversible. Cdk activity can be reactivated after dephosphorylation by Cdc25. The Cdc25 enzymes Cdc25A-C are known to control the transitions from G1 to S phase and G2 to M phase.[2]


Structure[edit] The structure of Cdc25 proteins can be divided into two main regions: the N-terminal region, which is highly divergent and contains sites for its phosphorylation and ubiquitination, which regulate the phosphatase activity; and the C-terminal region, which is highly homologous and contains the catalytic site.[3]


Evolution and species distribution[edit] 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.[4] 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.[5] 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[6] and meiosis,[7] 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).[8]


Knockout models[edit] 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,[9] 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.


In human disease[edit] The Cdc25s, and in particular Cdc25A and Cdc25B, are proto-oncogenes in humans and have been shown to be overexpressed in a number of cancers.[10] 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.[3] To date, no clinically viable compounds targeting these enzymes have been described. A large number of potent small-molecule Cdc25 Inhibitors have been identified that bind to the active site and belong to various chemical classes, including natural products, lipophilic acids, quinonoids, electrophiles, sulfonylated aminothiazoles and phosphate bioisosteres.[3] Although some progress has been made in developing potent and selective inhibitors for Cdc25 family of proteins, there is scope for development of novel therapeutic strategies to target them. A new class of peptide-derived inhibitors, based on sequence homology with the protein substrate, can be developed. It is challenging to use these compounds as drugs due to their lack of suitable ADME properties.[3]


See also[edit] Cyclin


References[edit] ^ Strausfeld U, Labbé JC, Fesquet D, et al. (May 1991). "Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein". Nature. 351 (6323): 242–5. doi:10.1038/351242a0. PMID 1828290.  ^ Morgan, David. The Cell Cycle: Principles of Control. London: New Science Press, 2007. 96-98, 34-35. Print. ^ a b c d Presentation on CDC25 PHOSPHATASES: A Potential Target for Novel Anticancer Agents ^ Sadhu K, Reed SI, Richardson H, Russell P (July 1990). "Human homolog of fission yeast cdc25 mitotic inducer is expressed predominantly in G2". Proc. Natl. Acad. Sci. U.S.A. 87 (13): 5139–43. doi:10.1073/pnas.87.13.5139. PMC 54277 . PMID 2195549.  ^ Landrieu I, da Costa M, De Veylder L, et al. (September 2004). "A small CDC25 dual-specificity tyrosine-phosphatase isoform in Arabidopsis thaliana". Proc. Natl. Acad. Sci. U.S.A. 101 (36): 13380–5. doi:10.1073/pnas.0405248101. PMC 516575 . PMID 15329414.  ^ Edgar BA, O'Farrell PH (April 1989). "Genetic Control of Cell Division Patterns in the Drosophila Embryo". Cell. 57 (1): 177–87. doi:10.1016/0092-8674(89)90183-9. PMC 2755076 . PMID 2702688.  ^ Alphey L, Jimenez J, White-Cooper H, Dawson I, Nurse P, Glover DM (June 1992). "twine, a cdc25 homolog that functions in the male and female germline of Drosophila". Cell. 69 (6): 977–88. doi:10.1016/0092-8674(92)90616-K. PMID 1606618.  ^ Ashcroft NR, Kosinski ME, Wickramasinghe D, Donovan PJ, Golden A (July 1998). "The four cdc25 genes from the nematode Caenorhabditis elegans". Gene. 214 (1–2): 59–66. doi:10.1016/S0378-1119(98)00228-5. PMID 9651482.  ^ Ferguson AM, White LS, Donovan PJ, Piwnica-Worms H (April 2005). "Normal Cell Cycle and Checkpoint Responses in Mice and Cells Lacking Cdc25B and Cdc25C Protein Phosphatases". Mol. Cell. Biol. 25 (7): 2853–60. doi:10.1128/MCB.25.7.2853-2860.2005. PMC 1061644 . PMID 15767688.  ^ Kristjánsdóttir K, Rudolph J (August 2004). "Cdc25 phosphatases and cancer". Chem. Biol. 11 (8): 1043–51. doi:10.1016/j.chembiol.2004.07.007. PMID 15324805. 


External links[edit] Genes[edit] CDC25A 1C25 Human cDc25A at PDB CDC25B CDC25C v t e Esterase: protein tyrosine phosphatases (EC 3.1.3.48) Class I Classical PTPs Receptor type PTPs PTPRA PTPRB PTPRC PTPRD PTPRE PTPRF PTPRG PTPRH PTPRJ PTPRK PTPRM PTPRN PTPRN2 PTPRO PTPRQ PTPRR PTPRS PTPRT PTPRU PTPRZ1 PTPRZ2 Non receptor type PTPs PTPN1 PTPN2 PTPN3 PTPN4 PTPN5 PTPN6 PTPN7 PTPN9 PTPN11 PTPN12 PTPN13 PTPN14 PTPN18 PTPN20 PTPN21 PTPN22 PTPN23 VH1-like or dual specific phosphatases (DSPs) MAPK phosphatases (MKPs) DUSP1 DUSP2 DUSP4 DUSP5 DUSP6 DUSP7 DUSP8 DUSP9 DUSP10 DUSP16 MK-STYX Slingshots SSH1 SSH2 SSH3 PRLs PTP4A1 PTP4A2 PTP4A3 CDC14s CDC14A CDC14B CDKN3 PTP9Q22 Atypical DSPs DUSP3 DUSP11 DUSP12 DUSP13A DUSP13B DUSP14 DUSP15 DUSP18 DUSP19 DUSP21 DUSP22 DUSP23 DUSP24 DUSP25 DUSP26 DUSP27 EMP2A RNGTT STYX Phosphatase and tensin homologs (PTENs) PTEN TPIP TPTE TNS TENC1 Myotubularins MTM1 MTMR2 MTMR3 MTMR4 MTMR5 MTMR6 MTMR7 MTMR8 MTMR9 MTMR10 MTMR11 MTMR12 MTMR13 MTMR14 MTMR15 Class II ACP1 Class III Cdc25 CDC25A CDC25B CDC25C Class IV EYA1 EYA2 EYA3 EYA4 v t e Cell cycle proteins Cyclin A (A1, A2) B (B1, B2, B3) D (D1, D2, D3) E (E1, E2) CDK 1 2 3 4 5 6 7 8 9 10 CDK-activating kinase CDK inhibitor INK4a/ARF (p14arf/p16, p15, p18, p19) cip/kip (p21, p27, p57) P53 p63 p73 family p53 p63 p73 Other Cdc2 Cdc25 Cdc42 Cellular apoptosis susceptibility protein E2F Maturation promoting factor Wee Cullin (CUL7) Phases and checkpoints Interphase G1 phase S phase G2 phase M phase Mitosis (Preprophase Prophase Prometaphase Metaphase Anaphase Telophase) Cytokinesis Cell cycle checkpoints Restriction point Spindle checkpoint Postreplication checkpoint Other cellular phases Apoptosis G0 phase Meiosis Retrieved from "https://en.wikipedia.org/w/index.php?title=Cdc25&oldid=786017819" Categories: EnzymesCell cycle


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Cdc25 - Photos and All Basic Informations

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PhosphataseSchizosaccharomyces PombeCell CycleCdc2Protein Tyrosine PhosphatasesCyclin-dependent KinaseMitosisCyclin Dependent KinasesCdk1Cyclin BWee1FungiYeastMetazoanPlantDual-specificity PhosphataseDrosophila MelanogasterMitosisMeiosisModel OrganismsCDC25CNematodeCaenorhabditis ElegansWee1OncogenesCancerPharmaceuticalChemotherapeuticCancerCyclinDigital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed CentralPubMed IdentifierDigital Object IdentifierPubMed CentralPubMed IdentifierDigital Object IdentifierPubMed CentralPubMed IdentifierDigital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed IdentifierDigital Object IdentifierPubMed CentralPubMed IdentifierDigital Object IdentifierPubMed IdentifierTemplate:Protein Tyrosine PhosphatasesTemplate Talk:Protein Tyrosine PhosphatasesEsteraseProtein Tyrosine PhosphataseEnzyme Commission NumberProtein Tyrosine PhosphataseReceptor Tyrosine PhosphatasePTPRAPTPRBPTPRCPTPRDPTPREPTPRFPTPRGPTPRHPTPRJPTPRKPTPRMPTPRNPTPRN2PTPROPTPRRPTPRSPTPRTPTPRUPTPRZ1PTPN1PTPN2PTPN3PTPN4PTPN5PTPN6PTPN7PTPN9PTPN11PTPN12PTPN13PTPN14PTPN18PTPN21PTPN22PTPN23Dual-specificity PhosphataseMAPK PhosphataseDUSP1DUSP2DUSP4DUSP5DUSP6DUSP7DUSP10DUSP16SSH1SSH2SSH3PTP4A1PTP4A2PTP4A3CDC14ACDC14BCDKN3DUSP3DUSP12DUSP15DUSP18DUSP19DUSP22DUSP23RNGTTPTEN (gene)TPTETENC1MyotubularinMyotubularin 1MTMR2MTMR3MTMR6MTMR9MTMR12MTMR14Protein Tyrosine PhosphataseACP1Protein Tyrosine PhosphataseCDC25ACDC25BCDC25CProtein Tyrosine PhosphataseEYA1EYA2EYA4Template:Cell Cycle ProteinsTemplate Talk:Cell Cycle ProteinsCell CycleProteinCyclinCyclin ACyclin A1Cyclin A2Cyclin BCyclin B1Cyclin B2Cyclin DCyclin D1Cyclin D2Cyclin D3Cyclin ECyclin E1Cyclin E2Cyclin-dependent KinaseCyclin-dependent Kinase 1Cyclin-dependent Kinase 2Cyclin-dependent Kinase 3Cyclin-dependent Kinase 4Cyclin-dependent Kinase 5Cyclin-dependent Kinase 6Cyclin-dependent Kinase 7Cyclin-dependent Kinase 8Cyclin-dependent Kinase 9Cyclin-dependent Kinase 10CDK-activating KinaseCyclin-dependent Kinase Inhibitor ProteinCell CycleP14arfP16CDKN2BCDKN2CCDKN2DCell CycleP21CDKN1BCyclin-dependent Kinase Inhibitor 1CP53 P63 P73 FamilyP53TP63P73Cdk1CDC42Cellular Apoptosis Susceptibility ProteinE2FMaturation Promoting FactorWee1CullinCUL7InterphaseG1 PhaseS PhaseG2 PhaseCell DivisionMitosisPreprophaseProphasePrometaphaseMetaphaseAnaphaseTelophaseCytokinesisCell Cycle CheckpointRestriction PointSpindle CheckpointPostreplication CheckpointApoptosisG0 PhaseMeiosisHelp:CategoryCategory:EnzymesCategory:Cell CycleDiscussion About Edits From This IP Address [n]A List Of Edits Made From This IP Address [y]View The Content Page [c]Discussion About The Content Page [t]Edit This Page [e]Visit The Main Page [z]Guides To Browsing WikipediaFeatured Content – The Best Of WikipediaFind Background Information On Current EventsLoad A Random Article [x]Guidance On How To Use And Edit WikipediaFind Out About WikipediaAbout The Project, What You Can Do, Where To Find ThingsA List Of Recent Changes In The Wiki [r]List Of All English Wikipedia Pages Containing Links To This Page [j]Recent Changes In Pages Linked From This Page [k]Upload Files [u]A List Of All Special Pages [q]Wikipedia:AboutWikipedia:General Disclaimer



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