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

Wanli Tang, Judy Qiju Wu, Chen Chen, Chih Sheng Yang, Jessie Yanxiang Guo, Christopher D. Freel, Sally Kornbluth

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2589-2597
Number of pages9
JournalMolecular biology of the cell
Volume21
Issue number15
DOIs
StatePublished - Aug 1 2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism'. Together they form a unique fingerprint.

Cite this