UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator

被引:36
作者
Walker, Adam
Acquaviva, Claire
Matsusaka, Takahiro
Koop, Lars
Pines, Jonathon [1 ]
机构
[1] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England
关键词
APC/C; mitosis; cyclin; cell cycle; ubiquitin;
D O I
10.1242/jcs.031591
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2319 / 2326
页数:8
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