Publications (6)55.77 Total impact
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Article: Inducible dissociation of SCF(Met30) ubiquitin ligase mediates a rapid transcriptional response to cadmium.
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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.The EMBO Journal 03/2005; 24(3):521-32. · 9.20 Impact Factor -
Article: Inducible dissociation of SCFMet30 ubiquitin ligase mediates a rapid transcriptional response to cadmium
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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.The EMBO Journal 01/2005; 24(3):521-532. · 9.20 Impact Factor -
Article: Dual regulation of the met4 transcription factor by ubiquitin-dependent degradation and inhibition of promoter recruitment.
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ABSTRACT: The ubiquitin system has been recently implicated in various aspects of transcriptional regulation, including proteasome-dependent degradation of transcriptional activators. In yeast, the activator Met4 is inhibited by the SCF(Met30) ubiquitin ligase, which recognizes and oligo-ubiquitylates Met4. Here, we demonstrate that in minimal media, Met4 is ubiquitylated and rapidly degraded in response to methionine excess, whereas in rich media, Met4 is oligo-ubiquitylated but remains stable. In the latter growth condition, oligo-ubiquitylated Met4 is not recruited to MET gene promoters, but is recruited to the SAM genes, which are required for production of S-adenosylmethionine, an unstable metabolite that is not present in rich medium. Thus, ubiquitylation not only regulates Met4 by distinct degradation-dependent and -independent mechanisms, but also controls differential recruitment of a single transcription factor to distinct promoters, thereby diversifying transcriptional activator specificity.Molecular Cell 08/2002; 10(1):69-80. · 14.18 Impact Factor -
Article: SCFMet30-mediated control of the transcriptional activator Met4 is required for the G1|[ndash]|S transition
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ABSTRACT: Progression through the cell cycle requires the coordination of basal metabolism with the cell cycle and growth machinery. Repression of the sulfur gene network is mediated by the ubiquitin ligase SCFMet30, which targets the transcription factor Met4p for degradation. Met30p is an essential protein in yeast. We have found that a met4met30 double mutant is viable, suggesting that the essential function of Met30p is to control Met4p. In support of this hypothesis, a Met4p mutant unable to activate transcription does not cause inviability in a met30 strain. Also, overexpression of an unregulated Met4p mutant is lethal in wild-type cells. Under non-permissive conditions, conditional met30 strains arrest as large, unbudded cells with 1N DNA content, at or shortly after the pheromone arrest point. met30 conditional mutants fail to accumulate CLN1 and CLN2, but not CLN3 mRNAs, even when CLN1 and CLN2 are expressed from strong heterologous promoters. One or more genes under the regulation of Met4p may delay the progression from G1 into S phase through specific regulation of critical G1 phase mRNAs.The EMBO Journal 04/2000; 19(7):1613-1624. · 9.20 Impact Factor -
Article: Feedback-regulated degradation of the transcriptional activator Met4 is triggered by the SCFMet30 complex
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ABSTRACT: Saccharomyces cerevisiae SCFMet30 ubiquitin–protein ligase controls cell cycle function and sulfur amino acid metabolism. We report here that the SCFMet30 complex mediates the transcriptional repression of the MET gene network by triggering degradation of the transcriptional activator Met4p when intracellular S-adenosylmethionine (AdoMet) increases. This AdoMet-induced Met4p degradation is dependent upon the 26S proteasome function. Unlike Met4p, the other components of the specific transcriptional activation complexes that are assembled upstream of the MET genes do not appear to be regulated at the protein level. We provide evidence that the interaction between Met4p and the F-box protein Met30p occurs irrespective of the level of intracellular AdoMet, suggesting that the timing of Met4p degradation is not controlled by its interaction with the SCFMet30 complex. We also demonstrate that Met30p is a short-lived protein, which localizes within the nucleus. Furthermore, transcription of the MET30 gene is regulated by intracellular AdoMet levels and is dependent upon the Met4p transcription activation function. Thus Met4p appears to control its own degradation by regulating the amount of assembled SCFMet30 ubiquitin ligase.The EMBO Journal 01/2000; 19(2):282-294. · 9.20 Impact Factor -
Article: Transport of Sulfonium Compounds
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ABSTRACT: We report here the characterization and the molecular analysis of the two high affinity permeases that mediate the transport of S-adenosylmethionine (AdoMet) andS-methylmethionine (SMM) across the plasma membrane of yeast cells. Mutant cells unable to use AdoMet as a sulfur source were first isolated and demonstrated to lack high affinity AdoMet transport capacities. Functional complementation cloning allowed us to identify the corresponding gene (SAM3), which encodes an integral membrane protein comprising 12 putative membrane spanning regions and belonging to the amino acid permease family. Among amino acid permease members, the closest relative of Sam3p is encoded by theYLL061w open reading frame. Disruption ofYLL061w was shown to specifically lead to cells unable to use SMM as a sulfur source. Accordingly, transport assays demonstrated that YLL061w disruption mutation impaired the high affinity SMM permease, and YLL061w was therefore renamedMMP1. Further study of sam3Δ andmmp1Δ mutant cells showed that in addition to high affinity permeases, both sulfonium compounds are transported into yeast cells by low affinity transport systems that appear to be carrier-facilitated diffusion.Journal of Biological Chemistry 09/1999; 274(40):28096-28105. · 4.77 Impact Factor
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Institutions
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1999–2005
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French National Centre for Scientific Research
- Centre de génétique moléculaire
Paris, Ile-de-France, France
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