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首页> 外文期刊>Cell cycle >An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast
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An E2 enzyme Ubc11 is required for ubiquitination of Slp1/Cdc20 and spindle checkpoint silencing in fission yeast

机译:E2酶Ubc11是裂变酵母中Slp1 / Cdc20泛素化和纺锤体检查点沉默所必需的

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For ordered mitotic progression, various proteins have to be regulated by an ubiquitin ligase, the anaphase-promoting complex or cyclosome (APC/C) with appropriate timing. Recent studies have implied that the activity of APC/C also contributes to release of mitotic checkpoint complexes (MCCs) from its target Cdc20 in the process of silencing the spindle assembly checkpoint (SAC). Here we describe a temperature-sensitive mutant (ubc11-P93L) in which cell cycle progression is arrested at mitosis. The mutant grows normally at the restrictive temperature when SAC is inactivated, suggesting that the arrest is not due to abnormal spindle assembly, but rather due to prolonged activation of SAC. Supporting this notion, MCCs remain bound to APC/C even when SAC is satisfied. The ubc11+ gene encodes one of the two E2 enzymes required for progression through mitosis in fission yeast. Remarkably, Slp1 (a fission yeast homolog of Cdc20), which is degraded in an APC/C-dependent manner, stays stable throughout the cell cycle in the ubc11-P93L mutant lacking the functional SAC. Other APC/C substrates, in contrast, were degraded on schedule. We have also found that a loss of Ubc4, the other E2 required for progression through mitosis, does not affect the stability of Slp1. We propose that each of the two E2 enzymes is responsible for collaborating with APC/C for a specific set of substrates, and that Ubc11 is responsible for regulating Slp1 with APC/C for silencing the SAC.
机译:对于有序的有丝分裂进程,必须在适当的时机通过泛素连接酶,后期促进复合物或环体(APC / C)调节各种蛋白质。最近的研究表明,APC / C的活性还有助于在使主轴装配检查点(SAC)沉默的过程中从其目标Cdc20释放有丝分裂检查点复合物(MCC)。在这里,我们描述了一个温度敏感型突变体(ubc11-P93L),其中细胞周期进程被阻止在有丝分裂状态。当SAC失活时,突变体在限制温度下正常生长,这表明逮捕不是由于异常的纺锤体组装,而是由于SAC的长时间激活。支持此概念的MCC仍然绑定到APC / C,即使满足SAC要求也是如此。 ubc11 +基因编码裂变酵母中通过有丝分裂进行进化所需的两种E2酶之一。值得注意的是,以APC / C依赖性方式降解的Slp1(Cdc20的裂变酵母同源物)在缺乏功能SAC的ubc11-P93L突变体中在整个细胞周期中保持稳定。相反,其他APC / C基板则按计划降解。我们还发现,Ubc4(通过有丝分裂进展所需的另一个E2)的丢失不会影响Slp1的稳定性。我们建议,这两种E2酶各自负责与APC / C协作进行特定底物组,而Ubc11则负责用APC / C调节Slp1以沉默SAC。

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