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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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
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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. |
format | Text |
id | pubmed-2912346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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