Inducible dissociation of SCF(Met30) ubiquitin ligase mediates a rapid transcriptional response to cadmium.
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.
Barbey
Régine
R
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvettte, France.
Baudouin-Cornu
Peggy
P
Lee
Traci A
TA
Rouillon
Astrid
A
Zarzov
Patrick
P
Tyers
Mike
M
Thomas
Dominique
D
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*
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