Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCF(Met30 )complex.
Saccharomyces cerevisiae SCF(Met30) ubiquitin-protein ligase controls cell cycle function and sulfur amino acid metabolism. We report here that the SCF(Met30 )complex mediates the transcriptional repression of the MET gene network by triggering degradation of the transcriptional activator Met4p when intracellular S-adenosylmethionine (AdoMet) increases. This AdoMet-induced Met4p degradation is dependent upon the 26S proteasome function. Unlike Met4p, the other components of the specific transcriptional activation complexes that are assembled upstream of the MET genes do not appear to be regulated at the protein level. We provide evidence that the interaction between Met4p and the F-box protein Met30p occurs irrespective of the level of intracellular AdoMet, suggesting that the timing of Met4p degradation is not controlled by its interaction with the SCF(Met30) complex. We also demonstrate that Met30p is a short-lived protein, which localizes within the nucleus. Furthermore, transcription of the MET30 gene is regulated by intracellular AdoMet levels and is dependent upon the Met4p transcription activation function. Thus Met4p appears to control its own degradation by regulating the amount of assembled SCF(Met30) ubiquitin ligase.
Rouillon
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A
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France.
Barbey
R
R
Patton
E E
EE
Tyers
M
M
Thomas
D
D
D050976:Basic-Leucine Zipper Transcription Factors; D019976:Cloning, Organism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli; D044783:F-Box Proteins; D005246:Feedback; D005656:Fungal Proteins / Q000378:metabolism*; D005838:Genotype; D005982:Glutathione Transferase / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D012436:S-Adenosylmethionine / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D005656:Fungal Proteins; C470285:MET30 protein, S cerevisiae; C073675:MET4 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D012436:S-Adenosylmethionine; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase; D008025:Ligases