title: Regulation of transcription by ubiquitination without proteolysis: Cdc34/SCF(Met30)-mediated inactivation of the transcription factor Met4.
abstract: Polyubiquitination of proteins by Cdc34/SCF complexes targets them for degradation by the 26S proteasome. The essential F-box protein Met30 is the substrate recognition subunit of the ubiquitin ligase SCF(Met30). The critical target of SCF(Met30) is the transcription factor Met4, as deletion of MET4 suppresses the lethality of met30 mutants. Surprisingly, Met4 is a relatively stable protein and its abundance is not influenced by Met30. However, transcriptional repression of Met4 target genes correlates with Cdc34/SCF(Met30)-dependent ubiquitination of Met4. Functionally, ubiquitinated Met4 associates with target promoters but fails to form functional transcription complexes. Our data reveal a novel proteolysis-independent function for Cdc34/SCF and indicate that ubiquitination of transcription factors can be utilized to directly regulate their activities.
authors.affiliation: The Scripps Research Institute, MB7, La Jolla, California, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kaiser
authors.forename: K
authors.initials: K
authors.lastname: Flick
authors.forename: C
authors.initials: C
authors.lastname: Wittenberg
authors.forename: S I
authors.initials: SI
authors.lastname: Reed
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D019757:Carbon-Oxygen Lyases / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D003547:Cysteine Synthase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044783:F-Box Proteins; D005656:Fungal Proteins / Q000378:metabolism; D008025:Ligases / Q000378:metabolism*; D008957:Models, Genetic; D009097:Multienzyme Complexes; D010453:Peptide Synthases / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; C064042:CBF1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D005656:Fungal Proteins; C470285:MET30 protein, S cerevisiae; C073675:MET4 protein, S cerevisiae; D009097:Multienzyme Complexes; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014452:Ubiquitins; C577449:CDC34 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D003547:Cysteine Synthase; C103381:MET17 protein, S cerevisiae; C018725:O-acetylhomoserine (thiol)-lyase; D019757:Carbon-Oxygen Lyases; D008025:Ligases; D010453:Peptide Synthases