<i>CDC20</i> and <i>CDH1</i> : A Family of Substrate-Specific Activators of APC-Dependent Proteolysis

TLDR

Proteolysis by the anaphase‑promoting complex (APC) drives chromosome segregation and mitotic exit, yet its regulation is poorly understood, and the conserved Cdc20 and Cdh1 proteins act as limiting, substrate‑specific activators. CDC20 is required for degrading the APC substrate Pds1 but not for Clb2 or Ase1, whereas cdh1Δ mutants fail to degrade Ase1 and Clb2 but not Pds1, and overexpression of either CDC20 or CDH1 can trigger APC‑dependent proteolysis of the appropriate target when it is normally stable.

Abstract

Proteolysis mediated by the anaphase-promoting complex (APC) triggers chromosome segregation and exit from mitosis, yet its regulation is poorly understood. The conserved Cdc20 and Cdh1 proteins were identified as limiting, substrate-specific activators of APC-dependent proteolysis. CDC20 was required for the degradation of the APC substrate Pds1 but not for that of other APC substrates, such as Clb2 and Ase1. Conversely, cdh1Delta mutants were impaired in the degradation of Ase1 and Clb2 but not in that of Pds1. Overexpression of either CDC20 or CDH1 was sufficient to induce APC-dependent proteolysis of the appropriate target in stages of the cell cycle in which substrates are normally stable.