CYCLIN-B PROTEOLYSIS AND THE CYCLIN-DEPENDENT KINASE INHIBITOR RUM1P ARE REQUIRED FOR PHEROMONE-INDUCED G(1) ARREST IN FISSION YEAST

The blocking of G(1) progression by fission yeast pheromones requires inhibition of the cyclin-dependent kinase cdc2p associated with the B- cyclins cdc13p and cig2p. We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin-assoc iated cdc2p kinase activity and for phermone-induced G(1) arrest. The cyclin-dependent kinase inhibitor rum1p is also required to maintain t his G(1) arrest; it binds both cdc13p and cig2p and is specifically re quired for cdc13p proteolysis. We propose that rum1p acts as an adapto r targeting cdc13p for degradation by the cyclosome. Ln contrast, the cig2p-cdc2p kinase can be down-regulated, and the cyclin cig2p can be proteolyzed independently of rum1p. We suggest that pheromone signalin g inhibits the cig2p-cdc2p kinase, bringing about a transient G(1) arr est. As a consequence, rumlp levels increase, thus inhibiting and indu cing proteolysis of the cdc13p-cdc2p kinase; this is necessary to main tain G(1) arrest. We have also shown that pheromone-induced transcript ion occurs only in G(1) and is independent of rum1p.