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DOI | 10.1038/s41467-017-02226-4 |
Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C | |
Zhang, Suyang1,2; Tischer, Thomas1; Barford, David1 | |
2019-08-27 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | England; Germany |
英文摘要 | The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C's activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000482711300005 |
WOS关键词 | ANAPHASE-PROMOTING COMPLEX ; CRYO-EM ; KEN-BOX ; DEPENDENT PROTEOLYSIS ; DEGRON RECOGNITION ; DESTRUCTION BOX ; CELL-CYCLE ; SUBSTRATE ; ACTIVATION ; MECHANISM |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203588 |
专题 | 资源环境科学 |
作者单位 | 1.MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England; 2.Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany |
推荐引用方式 GB/T 7714 | Zhang, Suyang,Tischer, Thomas,Barford, David. Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Zhang, Suyang,Tischer, Thomas,&Barford, David.(2019).Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C.NATURE COMMUNICATIONS,10. |
MLA | Zhang, Suyang,et al."Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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