CDC53P ACTS IN CONCERT WITH CDC4P AND CDC34P TO CONTROL THE G(1)-TO-S-PHASE TRANSITION AND IDENTIFIES A CONSERVED FAMILY OF PROTEINS

Regulation of cell cycle progression occurs in part through the target ed degradation of both activating and inhibitory subunits of the cycli n-dependent kinases. During G(1), CDC4, encoding a WD-40 repeat protei n, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the destruction of these regulators. Here we describe evidence indica ting that CDC53 also is involved in this process. Mutations in CDC53 c ause a phenotype indistinguishable from those of cdc4 and cdc34 mutati ons, numerous genetic interactions are seen between these genes, and t he encoded proteins are found physically associated in vivo. Cdc53p de fines a large family of proteins found in yeasts, nematodes, an humans whose molecular functions are uncharacterized. These results suggest a role for this family of proteins in regulating cell cycle proliferat ion through protein degradation.