An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination

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An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination

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Title: An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination
Author: Zeng, Xing; King, Randall Wharton

Note: Order does not necessarily reflect citation order of authors.

Citation: Zeng, Xing, and Randall W. King. 2012. An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination. Nature Chemical Biology 8(4): 383-392.
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Abstract: The Anaphase-Promoting Complex/Cyclosome (APC) is a ubiquitin ligase required for exit from mitosis. We previously showed that Tosyl Arginine Methyl Ester (TAME) inhibits APC-dependent proteolysis by competing with the C-terminal IR-tail of the APC activator Cdc20 for APC binding. Here we show that in the absence of APC substrates, TAME ejects Cdc20 from the APC by promoting Cdc20 auto-ubiquitination in its N-terminal region. Cyclin B1 antagonizes TAME's effect by promoting binding of free Cdc20 to the APC and suppressing Cdc20 auto-ubiquitination. Nevertheless, TAME stabilizes cyclin B1 in Xenopus extract by two mechanisms. First, it reduces the \(k_{cat}\) of the \(APC^{Cdc20}\)/cyclin B1 complex without affecting the \(K_m\), slowing the initial ubiquitination of unmodified cyclin B1. Second, as cyclin B1 becomes ubiquitinated, it loses its ability to promote Cdc20 binding to the APC in the presence of TAME. As a result, cyclin B1 ubiquitination terminates before reaching the threshold necessary for proteolysis.
Published Version: doi:10.1038/nchembio.801
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307893/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10532637
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