Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.

dc.contributor.author

Tang, Wanli

dc.contributor.author

Wu, Judy Qiju

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Chen, Chen

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Yang, Chih-Sheng

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Guo, Jessie Yanxiang

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Freel, Christopher D

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Kornbluth, Sally

dc.contributor.editor

Tansey, William P

dc.coverage.spatial

United States

dc.date.accessioned

2011-04-15T16:46:43Z

dc.date.issued

2010-08-01

dc.description.abstract

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.

dc.description.version

Version of Record

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/20534816

dc.identifier

E09-08-0708

dc.identifier.eissn

1939-4586

dc.identifier.uri

https://hdl.handle.net/10161/3328

dc.language

eng

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en_US

dc.publisher

American Society for Cell Biology (ASCB)

dc.relation.ispartof

Mol Biol Cell

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10.1091/mbc.E09-08-0708

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Molecular biology of the cell

dc.subject

Amino Acid Motifs

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Anaphase-Promoting Complex-Cyclosome

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Animals

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Biocatalysis

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Enzyme Activation

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F-Box Proteins

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Humans

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Protein Binding

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Structure-Activity Relationship

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Substrate Specificity

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Ubiquitin

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Ubiquitin-Conjugating Enzymes

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Ubiquitin-Protein Ligase Complexes

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Xenopus

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Xenopus Proteins

dc.title

Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.

dc.type

Journal article

duke.date.pubdate

2010-8-1

duke.description.issue

15

duke.description.volume

21

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/20534816

pubs.begin-page

2589

pubs.end-page

2597

pubs.issue

15

pubs.organisational-group

Basic Science Departments

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Pharmacology & Cancer Biology

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School of Medicine

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Staff

pubs.publication-status

Published

pubs.volume

21

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