Trinkle-Mulcahy Laura, Lamond Angus I
Division of Gene Regulation & Expression, School of Life Sciences, University of Dundee, Dow St., Dundee DD1 5EH, UK.
Curr Opin Cell Biol. 2006 Dec;18(6):623-31. doi: 10.1016/j.ceb.2006.09.001. Epub 2006 Oct 9.
Recent work has highlighted the important role played by protein phosphatase complexes in the regulation of mitosis from yeast to mammals. There have been important advances in defining the roles of the protein serine/threonine phosphatases PP1 and PP2A and the dual specificity protein tyrosine phosphatases CDC25 and Cdc14. Three independent studies defined a regulatory role for PP2A in the control of sister chromatid cohesion, involving a direct interaction with shugoshin. A chromatin targeting subunit has been identified for PP1 and the complex shown to play an essential role in chromosome segregation. Key regulatory residues within CDC25 have been mapped and its activity tied both to the initial activation of cyclin-dependent kinases at the centrosome and to DNA damage checkpoints. Novel roles have been defined for Cdc14, including regulation of rDNA and telomere segregation and participation in spindle assembly. These exciting advances show that protein phosphatases are not merely silent partners to kinases in regulating the control of cell division.
近期的研究突出了蛋白质磷酸酶复合物在从酵母到哺乳动物的有丝分裂调控中所起的重要作用。在确定蛋白质丝氨酸/苏氨酸磷酸酶PP1和PP2A以及双特异性蛋白质酪氨酸磷酸酶CDC25和Cdc14的作用方面取得了重要进展。三项独立研究确定了PP2A在姐妹染色单体黏连控制中的调节作用,涉及与守护蛋白的直接相互作用。已鉴定出PP1的一种染色质靶向亚基,且该复合物在染色体分离中起关键作用。已绘制出CDC25内的关键调节残基图谱,其活性与中心体处细胞周期蛋白依赖性激酶的初始激活以及DNA损伤检查点相关。已确定Cdc14的新作用,包括对核糖体DNA和端粒分离的调节以及参与纺锤体组装。这些令人兴奋的进展表明,蛋白质磷酸酶在调节细胞分裂控制中并非仅仅是激酶的沉默伙伴。