Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex
Abstract
The specificity of ubiquitin-mediated protein degradation with regards to the selection of substrates to be polyubiquitinated has only been determined rather recently. Substrate targeting by the N-end rule and HECT (homology to E6AP carboxylterminus) domain ubiquitin ligases occurs through substrate-specific binding domains. In contrast, the SCF complex recruits substrates through a substrate adaptor protein, the F-box subunit. Despite evidence showing that Cdc20 and Cdh1 bind and activate the anaphase-promoting complex (APC) in a substrate-specific manner, there is no evidence that the activating protein and substrate interact directly; hence, no clear model exists for the mechanism of APC activation or recruitment of substrates. We show here that the activators Cdc20 and Cdh1 can associate with substrates via their N termini. In the absence of APC, Cdc20 and Cdh1 bind substrates reflecting Cdc20–APC and Cdh1–APC specificity. The N termini of Cdc20 and Cdh1 provide specificity functionally, as demonstrated by the generation of active chimeras that display the specificity corresponding to their N termini. Thus, Cdc20 and Cdh1 act as both substrate recognition and activating modules for APC.
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Footnotes
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↵1 Present address: Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
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↵2 Corresponding author.
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E-MAIL marc{at}hms.harvard.edu; FAX (617) 432-2250.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.918201.
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- Received June 11, 2001.
- Accepted July 30, 2001.
- Cold Spring Harbor Laboratory Press