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  • 發布時間:2019-08-03 23:45 原文鏈接: RegulationofcellcycleprogressionbyPlk3

    The focus of this pathway is to illustrate the role of Polo-like Kinase 3 (Plk3 also known as Prk and Fnk) as part of the regulatory cascade leading to apoptosis and the arrest cell cycle progression prior to M phase. Phosphorlyation of Cdc25C on serine-216 causes the arrest of the cell cycle at the G2/M phase border by preventing Cdc25C from activating cyclinB1/Cdk1. Xie et al. demonstrated that Plk3 like Chk1 and Chk2 also phosphorlyates Cdc25C on serine-216 contributing to cell cycle arrest. Additionally they found that Plk3 also phosphorylates p53 on serine 20 at step that is stimulatory in the process leading up to p53-mediated apoptosis. Wang Q et al. found that Plk3 is closely associated with the centrosome and that this was dependent on the integrity of the microtubules. Expression of constitutively active or defective Plk3 kinase had significant defects on the shape and nature of the microtubule apparatus of the cell. In either case cell cycle progression was halted and apoptosis occurred.

    Contributor: Kosi Gramatikoff, PhD

    REFERENCES: Bulavin DV, Amundson SA, Fornace AJ. p38 and Chk1 kinases: different conductors for the G(2)/M checkpoint symphony. Curr Opin Genet Dev. 2002 Feb;12(1):92-7. Deming PB, Cistulli CA, Zhao H, Graves PR, Piwnica-Worms H, Paules RS, Downes CS, Kaufmann WK. The human decatenation checkpoint. Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12044-9. Hu B, Zhou XY, Wang X, Zeng ZC, Iliakis G, Wang Y. The radioresistance to killing of A1-5 cells derives from activation of the Chk1 pathway. J Biol Chem. 2001 May 25;276(21):17693-8. Liu HY, Nefsky BS, Walworth NC. The Ded1 DEAD box helicase interacts with Chk1 and Cdc2. J Biol Chem. 2002 Jan 25;277(4):2637-43. Mihaylov IS, Kondo T, Jones L, Ryzhikov S, Tanaka J, Zheng J, Higa LA, Minamino N, Cooley L, Zhang H. Control of DNA replication and chromosome ploidy by geminin and cyclin A. Mol Cell Biol. 2002 Mar;22(6):1868-80. ONeill T, Giarratani L, Chen P, Iyer L, Lee CH, Bobiak M, Kanai F, Zhou BB, Chung JH, Rathbun GA. Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach. J Biol Chem. 2002 May 3;277(18):16102-15. Savitsky PA, Finkel T. Redox regulation of Cdc25C. J Biol Chem. 2002 Jun 7;277(23):20535-40. Wang Q, Xie S, Chen J, Fukasawa K, Naik U, Traganos F, Darzynkiewicz Z, Jhanwar-Uniyal M, Dai W. Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol. 2002 May;22(10):3450-9. Weiss RS, Matsuoka S, Elledge SJ, Leder P. Hus1 acts upstream of chk1 in a mammalian DNA damage response pathway. Curr Biol. 2002 Jan 8;12(1):73-7. Xie S, Wang Q, Wu H, Cogswell J, Lu L, Jhanwar-Uniyal M, Dai W. Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated in part by polo-like kinase-3. J Biol Chem. 2001 Sep 28;276(39):36194-9. Xie S, Wu H, Wang Q, Cogswell JP, Husain I, Conn C, Stambrook P, Jhanwar-Uniyal M, Dai W. Plk3 functionally links DNA damage to cell cycle arrest and apoptosis at least in part via the p53 pathway. J Biol Chem. 2001 Nov 16;276(46):43305-12. Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC. BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet. 2002 Mar;30(3):285-9. Zhao H, Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol. 2001 Jul;21(13):4129-39.


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