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Journal Article

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

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Stark,  H.
Research Group of 3D Electron Cryo-Microscopy, MPI for biophysical chemistry, Max Planck Society;

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Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-8AF1-1
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.