Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex.
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 carboxyl terminus) 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.
Pubmed ID: 11562349 RIS Download
Amino Acid Sequence | Anaphase-Promoting Complex-Cyclosome | Cdc20 Proteins | Cdh1 Proteins | Cell Cycle Proteins | Fungal Proteins | Ligases | Molecular Sequence Data | Saccharomyces cerevisiae Proteins | Sequence Homology, Amino Acid | Substrate Specificity | Ubiquitin-Protein Ligase Complexes | Ubiquitin-Protein Ligases