期刊
GENES & DEVELOPMENT
卷 15, 期 24, 页码 3278-3285出版社
COLD SPRING HARBOR LAB PRESS
DOI: 10.1101/gad.945701
关键词
Emi1; Cdc20; Cdh1; APC; Mad2; mitosis
资金
- NIGMS NIH HHS [GM07365, GM54811, T32 GM007365, GM60489, R01 GM054811, R01 GM060439] Funding Source: Medline
The anaphase-promoting complex/cyclosome (APC) ubiquitin ligase is activated by Cdc20 and Cdh1 and inhibited by Mad2 and the spindle assembly checkpoint complex, Mad2B, and the early mitotic inhibitor Emi1. Mad2 inhibits APC(Cdc20), whereas Mad2B preferentially inhibits APC(Cdh1). We have examined the mechanism of APC inhibition by Emi1 and find that unlike Mad2 proteins, Emi1 binds and inhibits both APC(Cdh1) and APC(Cdc20). Also unlike Mad2, Emi1 stabilizes cyclin A in the embryo and requires zinc for its APC inhibitory activity. We find that Emi1 binds the substrate-binding region of Cdc20 and prevents substrate binding to the APC, illustrating a novel mechanism of APC inhibition.
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