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 | |
dc.contributor.author | Chen, Chen | |
dc.contributor.author | Yang, Chih-Sheng | |
dc.contributor.author | Guo, Jessie Yanxiang | |
dc.contributor.author | Freel, Christopher D | |
dc.contributor.author | 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 | ||
dc.identifier | E09-08-0708 | |
dc.identifier.eissn | 1939-4586 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.language.iso | en_US | |
dc.publisher | American Society for Cell Biology (ASCB) | |
dc.relation.ispartof | Mol Biol Cell | |
dc.relation.isversionof | 10.1091/mbc.E09-08-0708 | |
dc.relation.journal | Molecular biology of the cell | |
dc.subject | Amino Acid Motifs | |
dc.subject | Anaphase-Promoting Complex-Cyclosome | |
dc.subject | Animals | |
dc.subject | Biocatalysis | |
dc.subject | Enzyme Activation | |
dc.subject | F-Box Proteins | |
dc.subject | Humans | |
dc.subject | Protein Binding | |
dc.subject | Structure-Activity Relationship | |
dc.subject | Substrate Specificity | |
dc.subject | Ubiquitin | |
dc.subject | Ubiquitin-Conjugating Enzymes | |
dc.subject | Ubiquitin-Protein Ligase Complexes | |
dc.subject | Xenopus | |
dc.subject | 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 | ||
pubs.begin-page | 2589 | |
pubs.end-page | 2597 | |
pubs.issue | 15 | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Pharmacology & Cancer Biology | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Staff | |
pubs.publication-status | Published | |
pubs.volume | 21 |