Boutros Rose, Ducommun Bernard
LBCMCP-CNRS UMR5088-IFR109 "Institut d'Exploration Fonctionnelle des Génomes" University of Toulouse, Toulouse, France.
Cell Cycle. 2008 Feb 1;7(3):401-6. doi: 10.4161/cc.7.3.5295. Epub 2007 Nov 7.
The Cyclin-Dependent Kinase (CDK)-activating phosphatase CDC25B, localises to the centrosomes where its activity is both positively and negatively regulated by several kinases including Aurora A and CHK1. Our recent data also demonstrate a role for CDC25B in the centrosome duplication cycle and microtubule nucleation in interphase that appears to involve the recruitment of gamma-tubulin to the centrosomes. In the present study, we report that CDC25B, along with CHK1, CDK1 and WEE1, localize asymmetrically around the mother centrosome from S to G2-phases, and gradually become evenly distributed to the two centrosomes by late G2 phase, concomitant with centrosome maturation. We further demonstrate that siRNA inhibition of CDC25B results in an accumulation of cells in G2 phase with two separated centrosomes, each containing only a single centriole, suggesting a requirement for CDC25B in centriole duplication. We propose that the localisation of key cell cycle regulators to the mother centrosome ensures synchrony between the centrosome duplication and cell division cycles.
细胞周期蛋白依赖性激酶(CDK)激活磷酸酶CDC25B定位于中心体,在中心体其活性受到包括极光激酶A和CHK1在内的多种激酶的正负调控。我们最近的数据还表明,CDC25B在中心体复制周期和间期微管成核中发挥作用,这似乎涉及γ-微管蛋白向中心体的募集。在本研究中,我们报告,从S期到G2期,CDC25B与CHK1、CDK1和WEE1一起不对称地定位于母中心体周围,并在G2期末逐渐均匀分布到两个中心体,同时伴随着中心体成熟。我们进一步证明,siRNA抑制CDC25B会导致细胞在G2期积累,有两个分离的中心体,每个中心体仅含有一个中心粒,这表明中心粒复制需要CDC25B。我们提出,关键细胞周期调节因子定位于母中心体可确保中心体复制和细胞分裂周期之间的同步。