title: Inducible dissociation of SCF(Met30) ubiquitin ligase mediates a rapid transcriptional response to cadmium.
abstract: Activity of the Met4 transcription factor is antagonized by the SCF(Met30) ubiquitin ligase by degradation-dependent and degradation-independent mechanisms, in minimal and rich nutrient conditions, respectively. In this study, we show that the heavy metal Cd2+ over-rides both mechanisms to enable rapid Met4-dependent induction of metabolic networks needed for production of the antioxidant and Cd2+-chelating agent glutathione. Cd2+ inhibits SCF(Met30) activity through rapid dissociation of the F-box protein Met30 from the holocomplex. In minimal medium, dissociation of SCF(Met30) complex is sufficient to impair the methionine-induced degradation of Met4. In rich medium, dissociation of the SCF(Met30) complex is accompanied by a deubiquitylation mechanism that rapidly removes inhibitory ubiquitin moieties from Met4. Post-translational control of SCF(Met30) assembly by a physiological stress to allow rapid induction of a protective gene expression program represents a novel mode of regulation in the ubiquitin system.
authors.affiliation: Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvettte, France.
authors.forename: Régine
authors.initials: R
authors.lastname: Barbey
authors.forename: Peggy
authors.initials: P
authors.lastname: Baudouin-Cornu
authors.forename: Traci A
authors.initials: TA
authors.lastname: Lee
authors.forename: Astrid
authors.initials: A
authors.lastname: Rouillon
authors.forename: Patrick
authors.initials: P
authors.lastname: Zarzov
authors.forename: Mike
authors.initials: M
authors.lastname: Tyers
authors.forename: Dominique
authors.initials: D
authors.lastname: Thomas
mesh_terms: D002104:Cadmium / Q000494:pharmacology*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins; D008954:Models, Biological; D046912:Multiprotein Complexes; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D044783:F-Box Proteins; C470285:MET30 protein, S cerevisiae; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D002104:Cadmium; D043743:Ubiquitin-Protein Ligase Complexes