G1 cyclins CLN1 and CLN2 repress the mating factor response pathway at Start in the yeast cell cycle.
Transcriptional induction by the mating pheromone alpha-factor was monitored at different stages of the yeast cell cycle. G2/M-phase and pre-Start cells showed strong FUS1 mRNA induction, whereas in post-Start cells the signaling was reduced significantly. This reduction in signaling activity in post-Start cells was correlated with the presence of CLN1 or CLN2 transcripts and was not observed in synchronized cells lacking functional CLN1 and CLN2 genes. Activation of the Cln-Cdc28p kinase by overexpression of CLN2 from the GAL1 promoter strongly reduced FUS1 mRNA induction. CLN1 overexpression had a similar effect when the FAR1 gene, encoding a negative regulator of CLN1/2 function, was deleted. This reduction of pheromone signaling was specific for CLN1 and CLN2, as it was not observed when CLN3 was overexpressed. Inactivation of the Cln-Cdc28p kinase complex by thermal inactivation of temperature-sensitive Cdc28p prevented repression of FUS1 signaling. CLN2 overexpression suppressed the constitutive signaling and division-arrest phenotypes of cells with a disrupted gpa1 gene, indicating that the site of action for repression is downstream of the alpha-subunit (Gpa1p) of the heterotrimeric G protein. The repression at Start of pheromone signaling by Cln1-Cdc28p or Cln2-Cdc28p kinase complexes may contribute to the acquisition of pheromone resistance as cells execute Start.
Oehlen
L J
LJ
Rockefeller University, New York, New York 10021.
Cross
F R
FR
D001483:Base Sequence; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000235:genetics* / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D016193:G1 Phase; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins; D000072235:Mating Factor; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D010675:Pheromones / Q000494:pharmacology; D012331:RNA, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014158:Transcription, Genetic
C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; C081353:FAR1 protein, S cerevisiae; C490024:FUS1 protein, S cerevisiae; D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D008565:Membrane Proteins; D010455:Peptides; D010675:Pheromones; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000072235:Mating Factor; D017489:CDC28 Protein Kinase, S cerevisiae; D019204:GTP-Binding Proteins; C084293:GPA1 protein, S cerevisiae; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins