Inducible dissociation of SCFMet30 ubiquitin ligase mediates a rapid transcriptional response to cadmium

• Published in: The EMBO journal Vol. 24; no. 3; pp. 521 - 532
• Main Authors: Barbey, Régine, Baudouin-Cornu, Peggy, Lee, Traci A, Rouillon, Astrid, Zarzov, Patrick, Tyers, Mike, Thomas, Dominique
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 09-02-2005; Blackwell Publishing Ltd
• Subjects: Antioxidants; Cadmium; Chelating agents; Degradation; Heavy metals; ligase; methionine; Nutrients; Physiology; sulfur; ubiquitin
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600556

Activity of the Met4 transcription factor is antagonized by the SCFMet30 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 SCFMet30 activity through rapid dissociation of the F‐box protein Met30 from the holocomplex. In minimal medium, dissociation of SCFMet30 complex is sufficient to impair the methionine‐induced degradation of Met4. In rich medium, dissociation of the SCFMet30 complex is accompanied by a deubiquitylation mechanism that rapidly removes inhibitory ubiquitin moieties from Met4. Post‐translational control of SCFMet30 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.