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Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism

Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. Although the importance of Emi2 during oocyte maturation has been widely recognized and its regulation extensively studied, its mechanism of action remained elusive. Many APC/C i...

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Detalles Bibliográficos
Autores principales: Tang, Wanli, Wu, Judy Qiju, Chen, Chen, Yang, Chih-Sheng, Guo, Jessie Yanxiang, Freel, Christopher D., Kornbluth, Sally
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912346/
https://www.ncbi.nlm.nih.gov/pubmed/20534816
http://dx.doi.org/10.1091/mbc.E09-08-0708
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author Tang, Wanli
Wu, Judy Qiju
Chen, Chen
Yang, Chih-Sheng
Guo, Jessie Yanxiang
Freel, Christopher D.
Kornbluth, Sally
author_facet Tang, Wanli
Wu, Judy Qiju
Chen, Chen
Yang, Chih-Sheng
Guo, Jessie Yanxiang
Freel, Christopher D.
Kornbluth, Sally
author_sort Tang, Wanli
collection PubMed
description Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. Although the importance of Emi2 during oocyte maturation has been widely recognized and its regulation extensively studied, its mechanism of action remained elusive. Many APC/C inhibitors have been reported to act as pseudosubstrates, inhibiting the APC/C by preventing substrate binding. Here we show that a previously identified zinc-binding region is critical for the function of Emi2, whereas the D-box is largely dispensable. We further demonstrate that instead of acting through a “pseudosubstrate” mechanism as previously hypothesized, Emi2 can inhibit Cdc20-dependent activation of the APC/C substoichiometrically, blocking ubiquitin transfer from the ubiquitin-charged E2 to the substrate. These findings provide a novel mechanism of APC/C inhibition wherein the final step of ubiquitin transfer is targeted and raise the interesting possibility that APC/C is inhibited by Emi2 in a catalytic manner.
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spelling pubmed-29123462010-10-16 Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism Tang, Wanli Wu, Judy Qiju Chen, Chen Yang, Chih-Sheng Guo, Jessie Yanxiang Freel, Christopher D. Kornbluth, Sally Mol Biol Cell Articles Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. Although the importance of Emi2 during oocyte maturation has been widely recognized and its regulation extensively studied, its mechanism of action remained elusive. Many APC/C inhibitors have been reported to act as pseudosubstrates, inhibiting the APC/C by preventing substrate binding. Here we show that a previously identified zinc-binding region is critical for the function of Emi2, whereas the D-box is largely dispensable. We further demonstrate that instead of acting through a “pseudosubstrate” mechanism as previously hypothesized, Emi2 can inhibit Cdc20-dependent activation of the APC/C substoichiometrically, blocking ubiquitin transfer from the ubiquitin-charged E2 to the substrate. These findings provide a novel mechanism of APC/C inhibition wherein the final step of ubiquitin transfer is targeted and raise the interesting possibility that APC/C is inhibited by Emi2 in a catalytic manner. The American Society for Cell Biology 2010-08-01 /pmc/articles/PMC2912346/ /pubmed/20534816 http://dx.doi.org/10.1091/mbc.E09-08-0708 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Tang, Wanli
Wu, Judy Qiju
Chen, Chen
Yang, Chih-Sheng
Guo, Jessie Yanxiang
Freel, Christopher D.
Kornbluth, Sally
Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism
title Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism
title_full Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism
title_fullStr Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism
title_full_unstemmed Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism
title_short Emi2-mediated Inhibition of E2-substrate Ubiquitin Transfer by the Anaphase-promoting Complex/Cyclosome through a D-Box–independent Mechanism
title_sort emi2-mediated inhibition of e2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a d-box–independent mechanism
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912346/
https://www.ncbi.nlm.nih.gov/pubmed/20534816
http://dx.doi.org/10.1091/mbc.E09-08-0708
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