SCF(Met30)-mediated control of the transcriptional activator Met4 is required for the G(1)-S transition.
Progression through the cell cycle requires the coordination of basal metabolism with the cell cycle and growth machinery. Repression of the sulfur gene network is mediated by the ubiquitin ligase SCF(Met30), which targets the transcription factor Met4p for degradation. Met30p is an essential protein in yeast. We have found that a met4Deltamet30Delta double mutant is viable, suggesting that the essential function of Met30p is to control Met4p. In support of this hypothesis, a Met4p mutant unable to activate transcription does not cause inviability in a met30Delta strain. Also, overexpression of an unregulated Met4p mutant is lethal in wild-type cells. Under non-permissive conditions, conditional met30Delta strains arrest as large, unbudded cells with 1N DNA content, at or shortly after the pheromone arrest point. met30Delta conditional mutants fail to accumulate CLN1 and CLN2, but not CLN3 mRNAs, even when CLN1 and CLN2 are expressed from strong heterologous promoters. One or more genes under the regulation of Met4p may delay the progression from G(1) into S phase through specific regulation of critical G(1) phase mRNAs.
Patton
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EE
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Room 1078, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, Canada.
Peyraud
C
C
Rouillon
A
A
Surdin-Kerjan
Y
Y
Tyers
M
M
Thomas
D
D
D050976:Basic-Leucine Zipper Transcription Factors; D002455:Cell Division; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044783:F-Box Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal; D008025:Ligases / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D016196:S Phase / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D015534:Trans-Activators / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D050976:Basic-Leucine Zipper Transcription Factors; D016213:Cyclins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D005656:Fungal Proteins; C470285:MET30 protein, S cerevisiae; C073675:MET4 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D008025:Ligases