Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.
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.
Type
Journal articleSubject
Amino Acid MotifsAnaphase-Promoting Complex-Cyclosome
Animals
Biocatalysis
Enzyme Activation
F-Box Proteins
Humans
Protein Binding
Structure-Activity Relationship
Substrate Specificity
Ubiquitin
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligase Complexes
Xenopus
Xenopus Proteins
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https://hdl.handle.net/10161/3328Published Version (Please cite this version)
10.1091/mbc.E09-08-0708Publication Info
Tang, Wanli; Wu, Judy Qiju; Chen, Chen; Yang, Chih-Sheng; Guo, Jessie Yanxiang; Freel,
Christopher D; & Kornbluth, Sally (2010). Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting
complex/cyclosome through a D-box-independent mechanism. Mol Biol Cell, 21(15). pp. 2589-2597. 10.1091/mbc.E09-08-0708. Retrieved from https://hdl.handle.net/10161/3328.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Christopher Freel
Assoc VP, Research
Sally A. Kornbluth
Jo Rae Wright University Distinguished Professor Emerita
Our lab studies the regulation of complex cellular processes, including cell cycle
progression and programmed cell death (apoptosis). These tightly orchestrated processes
are critical for appropriate cell proliferation and cell death, and when they go awry
can result in cancer and degenerative disorders. Within these larger fields, we have
focused on understanding the cellular mechanisms that prevent the onset of mitosis
prior to the completion of DNA replication, the process
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