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- Title
Coactivator functions in a stoichiometric complex with anaphase-promoting complex/cyclosome to mediate substrate recognition.
- Authors
Passmore, Lori A.; Barford, David
- Abstract
The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit E3 ligase required for ubiquitin-dependent proteolysis of cell-cycle-regulatory proteins, including mitotic cyclins and securin/Pds1. Regulation of APC/C activity and substrate recognition, mediated by the coactivators Cdc20 and Cdh1, is fundamental to cell-cycle control. However, the precise mechanism by which coactivators stimulate APC/C ubiquitylation activity and the nature of the substrate-binding sites on the activated APC/C are not understood. Here, we show that the optimal interaction of substrate with APC/C is dependent specifically on the simultaneous association of coactivator. This is consistent with a model whereby both core APC/C subunits and coactivators contribute recognition sites for substrates, accounting for the bipartite nature (D and KEN boxes) of most APC/C degradation signals. A direct and stoichiometric function for the coactivators could explain how specific substrates are recognized by APC/C in a cell-cycle-specific manner, and how coactivator stimulates APC/C ubiquitylation activity.
- Subjects
LIGASES; ENZYMES; UBIQUITIN; PROTEINS; CYCLINS; GROWTH factors; CELL cycle; BIOLOGICAL rhythms
- Publication
EMBO Reports, 2005, Vol 6, Issue 9, p873
- ISSN
1469-221X
- Publication type
Article
- DOI
10.1038/sj.embor.7400482