title: Grr1-dependent inactivation of Mth1 mediates glucose-induced dissociation of Rgt1 from HXT gene promoters.
abstract: In budding yeast, HXT genes encoding hexose permeases are induced by glucose via a mechanism in which the F box protein Grr1 antagonizes activity of the transcriptional repressor Rgt1. Neither the mechanism of Rgt1 inactivation nor the role of Grr1 in that process has been understood. We show that glucose promotes phosphorylation of Rgt1 and its dissociation from HXT gene promoters. This cascade of events is dependent upon the F-box protein Grr1. Inactivation of Rgt1 is sufficient to explain the requirement for Grr1 but does not involve Rgt1 proteolysis or ubiquitination. We show that inactivation of Mth1 and Std1, known negative regulators of HXT gene expression, leads to the hyperphosphorylation of Rgt1 and its dissociation from HXT promoters even in the absence of glucose. Furthermore, inactivation of Mth1 and Std1 bypasses the requirement for Grr1 for induction of these events, suggesting they are targets for inactivation by Grr1. Consistent with that proposal, Mth1 is rapidly eliminated in response to glucose via a mechanism that requires Grr1. Based upon these data, we propose that glucose acts via Grr1 to promote the degradation of Mth1. Degradation of Mth1 leads to phosphorylation and dissociation of Rgt1 from HXT promoters, thereby activating HXT gene expression.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Flick
authors.forename: Nathalie
authors.initials: N
authors.lastname: Spielewoy
authors.forename: Tatyana I
authors.initials: TI
authors.lastname: Kalashnikova
authors.forename: Marisela
authors.initials: M
authors.lastname: Guaderrama
authors.forename: Qianzheng
authors.initials: Q
authors.lastname: Zhu
authors.forename: Hui-Chu
authors.initials: HC
authors.lastname: Chang
authors.forename: Curt
authors.initials: C
authors.lastname: Wittenberg
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C102114:RGT1 protein, S cerevisiae; D012097:Repressor Proteins; C081335:STD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C071032:GRR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D005947:Glucose