Cdc48p is required for the cell cycle commitment point at Start via degradation of the G1-CDK inhibitor Far1p.
Cdc48p is required for the cell cycle commitment point at Start via degradation of the G1-CDK inhibitor Far1p.
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DOI：
10.1083/jcb.200307025
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发表时间：
2003-10-13
影响因子：
7.8
通讯作者：
Liang, Chun
中科院分区：
文献类型：
--
作者：
Fu, Xinrong;Ng, Christine;Feng, Daorong;Liang, Chun
芽殖酵母CDC48P及其哺乳动物同源物p97参与了许多重要的细胞活动。由于以前的CDC48突变体具有排他性的G2/M期停滞，因此CDC48p被认为只在有丝分裂过程中发挥重要作用。我们发现，在正常的有丝分裂细胞周期中，CDC48P是执行START(一个相当于哺乳动物细胞中的限制点的酵母细胞周期承诺点)所必需的，也是在通过降解G1周期蛋白依赖的激酶抑制剂Far1p而退出交配信息素后，细胞周期重新进入细胞周期所必需的。我们的工作是第一次发现CDC48P作为G1期关键细胞周期调节因子的新角色，并揭示了Far1p的细胞周期调控，Far1p是第一个被证明是由CDC48P介导的必要蛋白分解事件的底物的细胞周期依赖激酶抑制剂。
The budding yeast Cdc48p and its mammalian homologue p97 are involved in many important cellular activities. Because previous cdc48 mutants have exclusive G2/M arrest, Cdc48p was thought to play an essential role only during mitosis. We found that Cdc48p is required for the execution of Start (a yeast cell cycle commitment point equivalent to the restriction point in mammalian cells) in both a normal mitotic cell cycle and cell cycle reentry after mating pheromone withdrawal through degradation of the G1–cyclin-dependent kinase inhibitor Far1p. Our work is the first to uncover novel roles of Cdc48p as a critical cell cycle regulator in G1, and to shed new light on cell cycle regulation of Far1p, which is the first cyclin-dependent kinase inhibitor shown to be a substrate of an essential proteolysis event mediated by Cdc48p.