UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator
UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator
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DOI：
10.1242/jcs.031591
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发表时间：
2008-07-15
影响因子：
4
通讯作者：
Pines, Jonathon
中科院分区：
文献类型：
--
作者：
Walker, Adam;Acquaviva, Claire;Pines, Jonathon
由后期促进复合体/环体（APC/C）泛素连接酶介导的泛素依赖性蛋白水解是细胞周期的核心。APC/C在有丝分裂和G1期靶向有丝分裂周期蛋白破坏，然后在S期灭活，从而产生有丝分裂和DNA复制交替所需的高、低周期蛋白cdk活性的交替状态。两个关键问题是APC/C如何被纺锤体组装检查点控制，以在染色体不正确附着的情况下延迟细胞有丝分裂，以及APC/C如何在细胞有丝分裂后失活。泛素结合蛋白UbcH10被认为是这两个问题的关键答案。然而，这里我们表明UbcH10的行为与纺锤体检查点和APC/C失活作为自主振荡器的一部分的关键作用不一致。相反，我们发现UbcH10的限速作用仅在G1期结束，就在DNA复制开始之前。
Ubiquitin-dependent proteolysis mediated by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase lies at the heart of the cell cycle. The APC/C targets mitotic cyclins for destruction in mitosis and G1 phase and is then inactivated at S phase, thereby generating the alternating states of high and low cyclin-Cdk activity required for the alternation of mitosis and DNA replication. Two key questions are how the APC/C is held in check by the spindle-assembly checkpoint to delay cells in mitosis in the presence of improperly attached chromosomes, and how the APC/C is inactivated once cells exit mitosis. The ubiquitin-conjugating protein UbcH10 has been proposed to be crucial in the answers to both questions. However, here we show that the behaviour of UbcH10 is inconsistent with both a crucial role in the spindle checkpoint and in inactivating the APC/C as part of an autonomous oscillator. Instead, we find that the rate-limiting role of UbcH10 is only at the end of G1 phase, just before DNA replication begins.