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  APC15 mediates CDC20 autoubiquitylation by APC/C-MCC and disassembly of the mitotic checkpoint complex.

Uzunova, K., Dye, B. T., Schutz, H., Ladurner, R., Petzold, G., Toyoda, Y., et al. (2012). APC15 mediates CDC20 autoubiquitylation by APC/C-MCC and disassembly of the mitotic checkpoint complex. Nature Structural and Molecular Biology, 19(11), 1116-1123. doi:10.1038/nsmb.2412.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8AF1-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-1DE6-3
Genre: Journal Article

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 Creators:
Uzunova, K., Author
Dye, B. T., Author
Schutz, H., Author
Ladurner, R., Author
Petzold, G., Author
Toyoda, Y., Author
Jarvis, M. A., Author
Brown, N. G., Author
Poser, I., Author
Novatchkova, M., Author
Mechtler, K., Author
Hyman, A. A., Author
Stark, H.1, Author              
Schulman, B. A., Author
Peters, J. M., Author
Affiliations:
1Research Group of 3D Electron Cryo-Microscopy, MPI for biophysical chemistry, Max Planck Society, ou_578577              

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 Abstract: The anaphase-promoting complex/cyclosome (APC/C) bound to CDC20 (APC/C-CDC20) initiates anaphase by ubiquitylating B-type cyclins and securin. During chromosome bi-orientation, CDC20 assembles with MAD2, BUBR1 and BUB3 into a mitotic checkpoint complex (MCC) that inhibits substrate recruitment to the APC/C. APC/C activation depends on MCC disassembly, which was proposed to require CDC20 autoubiquitylation. Here we characterize APC15, a human APC/C subunit related to yeast Mnd2. APC15 is located near APC/C's MCC binding site; it is required for APC/C-bound MCC (APC/C-MCC)-dependent CDC20 autoubiquitylation and degradation and for timely anaphase initiation but is dispensable for substrate ubiquitylation by APC/C-CDC20 and APC/C-CDH1. Our results support the model wherein MCC is continuously assembled and disassembled to enable rapid activation of APC/C-CDC20 and CDC20 autoubiquitylation promotes MCC disassembly. We propose that APC15 and Mnd2 negatively regulate APC/C coactivators and report generation of recombinant human APC/C.

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Language(s): eng - English
 Dates: 2012-09-242012-11
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1038/nsmb.2412
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Title: Nature Structural and Molecular Biology
Source Genre: Journal
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Pages: - Volume / Issue: 19 (11) Sequence Number: - Start / End Page: 1116 - 1123 Identifier: -