Proteolysis mediated by the anaphase-promoting complex (APC) triggers
chromosome segregation and exit from mitosis, yet its regulation is po
orly understood. The conserved Cdc20 and Cdh1 proteins were identified
as limiting, substrate-specific activators of APC-dependent proteolys
is. CDC20 was required for the degradation of the APC substrate Pds1 b
ut not for that of other APC substrates, such as Clb2 and Ase1. Conver
sely, cdh1 Delta mutants were impaired in the degradation of Ase1 and
Clb2 but not in that of Pds1. Overexpression of either CDC20 or CDH1 w
as sufficient to induce APC-dependent proteolysis of the appropriate t
arget in stages of the cell cycle in which substrates are normally sta
ble.