期刊
CELL
卷 124, 期 2, 页码 367-380出版社
CELL PRESS
DOI: 10.1016/j.cell.2005.10.038
关键词
-
资金
- NCI NIH HHS [CA09302] Funding Source: Medline
- NIGMS NIH HHS [R01 GM73023, R01 GM54811, R01 GM060439] Funding Source: Medline
The anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 controls progression to S phase and mitosis by stabilizing key APC/C ubiquitination substrates, including cyclin A. Examining Emi1 binding proteins, we identified the Evi5 oncogene as a regulator of Emi1 accumulation. Evi5 antagonizes SCF beta TrCP-dependent Emi1 ubiquitination and destruction by binding to a site adjacent to Emi1's DSGxxS degron and blocking both degron phosphorylation by Polo-like kinases and subsequent beta TrCP binding. Thus, Evi5 functions as a stabilizing factor maintaining Emi1 levels in S/G2 phase. Evi5 protein accumulates in early G1 following Plk1 destruction and is degraded in a Plk1 - and ubiquitin-dependent manner in early mitosis. Ablation of Evi5 induces precocious degradation of Emi1 by the Plk/SCF beta TrCP pathway, causing premature APC/C activation; cyclin destruction; cell-cycle arrest; centrosome overduplication; and, finally, mitotic catastrophe. We propose that the balance of Evi5 and Pololike kinase activities determines the timely accumulation of Emi1 and cyclin, ensuring mitotic fidelity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据