Ren Shengjun, Rollins Barrett J
Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell. 2004 Apr 16;117(2):239-51. doi: 10.1016/s0092-8674(04)00300-9.
G0 is a physiological state occupied by resting or terminally differentiated cells that have exited the cell cycle. In contrast to the well-characterized cyclin/cdk-mediated inactivation of pRb that controls the G1/S transition, little is known about regulation of the G0/G1 transition. However, pRb is likely to participate in this process because its acute somatic inactivation is sufficient for G0-arrested cells to re-enter the cell cycle. One physiological regulator of this event may be cyclin C because its highest mRNA levels occur during G0 exit. Here we show that a non-cdk8-associated cellular pool of cyclin C combines with cdk3 to stimulate pRb phosphorylation at S807/811 during the G0/G1 transition, and that this phosphorylation is required for cells to exit G0 efficiently. Thus, G1 entry is regulated in an analogous fashion to S phase entry, but involves a distinct cyclin/cdk combination.
G0是一种生理状态，由已退出细胞周期的静止或终末分化细胞占据。与控制G1/S转换的、特征明确的细胞周期蛋白/细胞周期蛋白依赖性激酶（cyclin/cdk）介导的视网膜母细胞瘤蛋白（pRb）失活不同，人们对G0/G1转换的调控知之甚少。然而，pRb可能参与了这一过程，因为其急性体细胞失活足以使G0期停滞的细胞重新进入细胞周期。该事件的一种生理调节因子可能是细胞周期蛋白C，因为其最高mRNA水平出现在G0期退出期间。我们在此表明，细胞周期蛋白C的一个与细胞周期蛋白依赖性激酶8（cdk8）无关的细胞池在G0/G1转换期间与细胞周期蛋白依赖性激酶3（cdk3）结合，以刺激pRb在S807/811位点的磷酸化，并且这种磷酸化是细胞有效退出G0所必需的。因此，G1期进入的调控方式与S期进入类似，但涉及一种不同 的细胞周期蛋白/细胞周期蛋白依赖性激酶组合。
