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TitleAPC15 mediates CDC20 autoubiquitylation by APC/C(MCC) and disassembly of the mitotic checkpoint complex.
Journal, issue, pagesNat Struct Mol Biol, Vol. 19, Issue 11, Page 1116-1123, Year 2012
Publish dateSep 24, 2012
AuthorsKristina Uzunova / Billy T Dye / Hannelore Schutz / Rene Ladurner / Georg Petzold / Yusuke Toyoda / Marc A Jarvis / Nicholas G Brown / Ina Poser / Maria Novatchkova / Karl Mechtler / Anthony A Hyman / Holger Stark / Brenda A Schulman / Jan-Michael Peters /
PubMed AbstractThe 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 ...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.
External linksNat Struct Mol Biol / PubMed:23007861 / PubMed Central
MethodsEM (single particle)
Resolution30.0 Å
Structure data

EMDB-2204:
APC15 mediates CDC20 auto-ubiquitylation by APC/CMCC and MCC disassembly
Method: EM (single particle) / Resolution: 30.0 Å

Source
  • Homo sapiens (human)

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