Article
- The EMBO Journal (2005) 24, 521 - 532
- doi:10.1038/sj.emboj.7600556
Published online: 20 January 2005
Subject Categories:
Inducible dissociation of SCFMet30 ubiquitin ligase mediates a rapid transcriptional response to cadmium
Régine Barbey1,a, Peggy Baudouin-Cornu1,2,a, Traci A Lee2,a, Astrid Rouillon3, Patrick Zarzov3, Mike Tyers2 and Dominique Thomas1,3
- Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvettte, France
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
- Cytomics Systems SA, Gif sur Yvette, France
Correspondence to:
Dominique Thomas, Cytomics Systems, Bat 5, Avenue de la Terrasse, 91198 Gif-sur-Yvettte, France. Tel.: +33 1 6982 4266; Fax: +33 1 6982 4372; E-mail: dthomas@cytomics.fr
aThese authors contributed equally to this work
Received 11 October 2004; Accepted 22 December 2004
Abstract
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.
Keywords:
- cadmium,
- ligase,
- methionine,
- sulfur,
- ubiquitin
