title: Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle.
abstract: Grr1 protein of the yeast Saccharomyces cerevisiae is a central component of a glucose signal transduction mechanism responsible for glucose-induced gene expression. It is required for glucose-stimulated regulation of Rgt1, a repressor of several glucose-induced HXT genes. Grr1 also plays a role in regulating the cell cycle, because it is required for degradation of the G1 cyclins Cln1 and Cln2. We discovered that Grr1 physically interacts with Skp1, a protein that has been implicated in a ubiquitin-conjugating enzyme complex that targets for degradation the cell cycle regulators Cln1 and Cln2, and the cyclin-dependent kinase inhibitor Sic1. Thus, Grr1 may regulate the cell cycle and glucose-induced gene expression via ubiquitin-mediated protein degradation. Consistent with this idea, Skp1, like Grr1, was found to be required for glucose-induced HXT gene expression. Two functional domains of Grr1 are required for its interaction with Skp1: 12 leucine-rich repeats (LRR) and an adjacent F-box. The Grr1-Skp1 interaction is enhanced by high levels of glucose. This could provide yeast with a mechanism for coupling nutrient availability to gene expression and cell cycle regulation.
authors.affiliation: Department of Genetics, Box 8232, Washington University, School of Medicine, St Louis, MO 63110, USA.
authors.forename: F N
authors.initials: FN
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Johnston
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D044783:F-Box Proteins; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005816:Genetic Complementation Test; D005838:Genotype; D005947:Glucose / Q000494:pharmacology; D008025:Ligases / Q000378:metabolism; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
chemical_list: C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D044783:F-Box Proteins; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D044786:S-Phase Kinase-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C071032:GRR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D005947:Glucose