Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins.
Cell cycle progression in eukaryotes is controlled by the p34cdc2/CDC28 protein kinase and its short-lived, phase-specific regulatory subunits called cyclins. 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. 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, and CLB2, an M-phase cyclin, 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. Thus distinct degradation signals or regulated interaction with the ubiquitin-protein ligase system may determine the cell-cycle specificity of cyclin proteolysis.
Seufert
W
W
Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Tübingen, Germany.
Futcher
B
B
Jentsch
S
S
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D019926:Cyclin B; D016213:Cyclins / Q000378:metabolism*; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D008025:Ligases / Q000235:genetics*; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D014981:Xenopus; D000098843:Ubiquitin-Conjugating Enzyme UBC9
C076558:CLB5 protein, S cerevisiae; D019926:Cyclin B; D016213:Cyclins; D004271:DNA, Fungal; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9