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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Tang, W; Wu, JQ; Chen, C; Yang, C-S; Guo, JY; Freel, CD; Kornbluth, S

Published Date

  • August 2010

Published In

Volume / Issue

  • 21 / 15

Start / End Page

  • 2589 - 2597

PubMed ID

  • 20534816

Pubmed Central ID

  • PMC2912346

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

International Standard Serial Number (ISSN)

  • 1059-1524

Digital Object Identifier (DOI)

  • 10.1091/mbc.e09-08-0708


  • eng