Identification of multiple CDH1 homologues in vertebrates conferring different substrate specificities

CDC20/CDH1 activates the anaphase-promoting complex (APC) and targets vario us substrates for degradation, thereby allowing the ordered progression thr ough mitosis and G(1). We have found multiple functional CDH1 homologues in the chick. The transcripts of these novel genes are differentially localiz ed to proliferating, differentiated, and postmitotic tissues. All four prot eins bind and form a complex with APC in vitro and in cultural cells and ha ve quantitatively different activities in mediating ubiquitination of vario us APC substrates. Our results suggest that multiple CDH1s may temporally a nd spatially regulate APC activity both within and outside of the cell cycl e.