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.
Mesh Terms:
Cadmium, DNA, Fungal, F-Box Proteins, Models, Biological, Multiprotein Complexes, Oxidative Stress, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic, Ubiquitin, Ubiquitin-Protein Ligase Complexes
Cadmium, DNA, Fungal, F-Box Proteins, Models, Biological, Multiprotein Complexes, Oxidative Stress, Protein Processing, Post-Translational, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic, Ubiquitin, Ubiquitin-Protein Ligase Complexes
EMBO J.
Date: Feb. 09, 2005
PubMed ID: 15660125
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