Emi1通过与Mad2蛋白不同的机制调控后期促进复合物。
Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins.
作者信息
Reimann J D, Gardner B E, Margottin-Goguet F, Jackson P K
机构信息
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
出版信息
Genes Dev. 2001 Dec 15;15(24):3278-85. doi: 10.1101/gad.945701.
Abstract
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.
摘要
后期促进复合物/环体（APC）泛素连接酶由Cdc20和Cdh1激活，并受到Mad2、纺锤体组装检查点复合物Mad2B以及早期有丝分裂抑制剂Emi1的抑制。Mad2抑制APC（Cdc20），而Mad2B优先抑制APC（Cdh1）。我们研究了Emi1抑制APC的机制，发现与Mad2蛋白不同，Emi1结合并抑制APC（Cdh1）和APC（Cdc20）。同样与Mad2不同的是，Emi1在胚胎中稳定细胞周期蛋白A，并且其APC抑制活性需要锌。我们发现Emi1结合Cdc20的底物结合区域并阻止底物与APC结合，阐明了一种APC抑制的新机制。
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Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1.有丝分裂检查点蛋白BubR1对后期促进复合物Cdc20的Mad2非依赖性抑制作用。
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