Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex

The specificity of ubiquitin-mediated protein degradation with regards to t he 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 substrat e-specific binding domains. In contrast, the SCF complex recruits substrate s through a substrate adaptor protein, the F-box subunit. Despite evidence showing that Cdc20 and Cdh1 bind and activate the anaphase-promoting comple x (APC) in a substrate-specific manner, there is no evidence that the activ ating 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 t heir N termini. In the absence of APC, Cdc20 and Cdh1 bind substrates refle cting Cdc20-APC and Cdh1-APC specificity. The N termini of Cdc20 and Cdh1 p rovide specificity functionally, as demonstrated by the generation of activ e chimeras that display the specificity corresponding to their N termini. T hus, Cdc20 and Cdh1 act as both substrate recognition and activating module s for APC.