ROLE OF A UBIQUITIN-CONJUGATING ENZYME IN DEGRADATION OF S-PHASE AND M-PHASE CYCLINS

CELL cycle progression in eukaryotes is controlled by the p34(cdc2/CDC28) protein kinase and its short-lived, phase-specific regulatory subunits called cyclins(1,2). In Xenopus oocytes, degradation of M-phase (B-type) cyclins is required for exit from mitosis and is mediated by the ubiquitin-dependent proteolytic system(3). Here we show that B-type-cyclin degradation in yeast involves an essential nuclear ubiquitin-conjugating enzyme, UBC9. Repression of UBC9 synthesis prevents cell cycle progression at the G2 or early M phase, causing the accumulation of large budded cells with a single nucleus, a short spindle and replicated DNA. In ubc9 mutants both CLB5, an S-phase cyclin(4,5), and CLB2, an M-phase cyclin(6,7), are stabilized. In wild-type cells the CLB5 protein is unstable throughout the cell cycle, whereas CLB2 turnover occurs only at a specific cell-cycle stage(8). Thus distinct degradation signals or regulated interaction,vith the ubiquitin-protein ligase system may determine the cell-cycle specificity of cyclin proteolysis.