title: The ubiquitin ligase SCFGrr1 is necessary for pheromone sensitivity in Saccharomyces cerevisiae.
abstract: The presence of the appropriate pheromone induces alpha and a cells of the yeast Saccharomyces cerevisiae to activate both changes in transcriptional expression and cell polarity that eventually lead to the mating of alpha and a cells to form a/alpha diploid cells. A third response after exposure to mating pheromone is a transient cell cycle arrest, allowing synchronization of the two cell types in G1 prior to cell fusion. At least in part, this cell cycle arrest requires the inactivation of Cln-kinase activity through transcriptional inactivation of the CLN1 and CLN2 genes, degradation of the Cln proteins and direct inhibition of Cln-kinase complexes. Here we report that GRR1, which encodes a substrate recognition subunit of SCF complexes, is critical for pheromone sensitivity and likely for this arrest. Loss of SCF(Grr1) function by deletion of the GRR1 gene causes pheromone resistance. However, deletion of CLN1 and CLN2 restores pheromone sensitivity to grr1Delta cells. Thus, rapid loss of Cln-kinase activity during mating may require coordinated inactivation of the Cln-kinase complexes, inactivation of CLN transcription and SCF(Grr1)-dependent Cln degradation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Schweitzer
authors.forename: Ross
authors.initials: R
authors.lastname: Cocklin
authors.forename: Lisa
authors.initials: L
authors.lastname: Garrett
authors.forename: Falguni
authors.initials: F
authors.lastname: Desai
authors.forename: Mark
authors.initials: M
authors.lastname: Goebl
mesh_terms: D000626:Aminopeptidases; D002453:Cell Cycle / Q000187:drug effects; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D010450:Endopeptidases; D044783:F-Box Proteins; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D010675:Pheromones / Q000494:pharmacology*; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D057057:Serine Proteases; D000091346:Tripeptidyl-Peptidase 1; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C082719:CLN1 protein, S cerevisiae; D016213:Cyclins; D044783:F-Box Proteins; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D000091346:Tripeptidyl-Peptidase 1; C071032:GRR1 protein, S cerevisiae; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; D010447:Peptide Hydrolases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases