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

C. M. Pfleger, E. Lee, M. W. Kirschner

Research output: Contribution to journalArticlepeer-review

204 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)2396-2407
Number of pages12
JournalGenes and Development
Volume15
Issue number18
DOIs
StatePublished - 15 Sep 2001
Externally publishedYes

Keywords

  • APC
  • Binding
  • Cdc20
  • Cdh1
  • Substrate

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