Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae.
Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae.
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DOI：
10.1016/j.cellsig.2017.02.003
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发表时间：
2017-05
影响因子：
4.8
通讯作者：
Solomon MJ
中科院分区：
文献类型：
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作者：
Wang R;Burton JL;Solomon MJ
后期促进复合体(APC)是一种泛素连接酶，负责促进许多细胞周期调节因子的降解。APC的激活剂和底物结合蛋白之一是CDC20。已有研究表明，在正常细胞中，CdC20主要通过顺式降解方式(即通过分子内机制)促进APC自身的降解。然而，在主轴组件检查点(SAC)期间，Cdc20是如何降解的仍不完全清楚。在这项研究中，我们使用双镉系统来研究这一问题，发现顺式降解模式也是导致镉在SAC过程中降解的主要途径。此外，我们还发现，APCCDc20活性与CDC20启动子的转录活性之间存在负相关关系，这可能是通过APCCDc20底物，如周期蛋白Clb2和Clb5的反馈调节而发生的。这些发现有助于我们理解如何抑制APCCDC20活性和促进CDC20降解是正确的纺锤体检查点停止所必需的。
The anaphase-promoting complex (APC) is a ubiquitin ligase responsible for promoting the degradation of many cell cycle regulators. One of the activators and substrate-binding proteins for the APC is Cdc20. It has been shown previously that Cdc20 can promote its own degradation by the APC in normal cycling cells mainly through a cis-degradation mode (i.e. via an intramolecular mechanism). However, how Cdc20 is degraded during the spindle assembly checkpoint (SAC) is still not fully clear. In this study, we used a dual-Cdc20 system to investigate this issue and found that the cis-degradation mode is also the major pathway responsible for Cdc20 degradation during the SAC. In addition, we found that there is an inverse relationship between APCCdc20 activity and the transcriptional activity of the CDC20 promoter, which likely occurs through feedback regulation by APCCdc20 substrates, such as the cyclins Clb2 and Clb5. These findings contribute to our understanding of how the inhibition of APCCdc20 activity and enhanced Cdc20 degradation are required for proper spindle checkpoint arrest.