Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.
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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.
SubjectAmino Acid Motifs
Ubiquitin-Protein Ligase Complexes
Published Version (Please cite this version)10.1091/mbc.E09-08-0708
Publication InfoTang, W; Wu, JQ; Chen, C; Yang, CS; Guo, JY; Freel, CD; & Kornbluth, S (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 http://hdl.handle.net/10161/3328.
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Jo Rae Wright University Professor
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