Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p.
In Saccharomyces cerevisiae, mating pheromones activate two MAP kinases (MAPKs), Fus3p and Kss1p, to induce G1 arrest prior to mating. Fus3p is known to promote G1 arrest by activating Far1p, which inhibits three Clnp/Cdc28p kinases. To analyze the contribution of Fus3p and Kss1p to G1 arrest that is independent of ... Far1p, we constructed far1 CLN strains that undergo G1 arrest from increased activation of the mating MAP kinase pathway. We find that Fus3p and Kss1p both control G1 arrest through multiple functions that operate in parallel with Far1p. Fus3p and Kss1p together promote G1 arrest by repressing transcription of G1/S cyclin genes (CLN1, CLN2, CLB5) by a mechanism that blocks their activation by Cln3p/Cdc28p kinase. In addition, Fus3p and Kss1p counteract G1 arrest through overlapping and distinct functions. Fus3p and Kss1p together increase the expression of CLN3 and PCL2 genes that promote budding, and Kss1p inhibits the MAP kinase cascade. Strikingly, Fus3p promotes proliferation by a novel function that is not linked to reduced Ste12p activity or increased levels of Cln2p/Cdc28p kinase. Genetic analysis suggests that Fus3p promotes proliferation through activation of Mcm1p transcription factor that upregulates numerous genes in G1 phase. Thus, Fus3p and Kss1p control G1 arrest through a balance of arrest functions that inhibit the Cdc28p machinery and proliferative functions that bypass this inhibition.
Mesh Terms:
Aspartic Acid Endopeptidases, Blotting, Northern, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle, Cell Cycle Proteins, Crosses, Genetic, Cyclin-Dependent Kinase Inhibitor Proteins, Cyclins, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Fungal Proteins, G1 Phase, Gene Expression, Gene Expression Regulation, Fungal, Genotype, Immunoblotting, Mitogen-Activated Protein Kinases, Models, Biological, Peptides, Repressor Proteins, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Suppression, Genetic, beta-Galactosidase
Aspartic Acid Endopeptidases, Blotting, Northern, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle, Cell Cycle Proteins, Crosses, Genetic, Cyclin-Dependent Kinase Inhibitor Proteins, Cyclins, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Fungal Proteins, G1 Phase, Gene Expression, Gene Expression Regulation, Fungal, Genotype, Immunoblotting, Mitogen-Activated Protein Kinases, Models, Biological, Peptides, Repressor Proteins, S Phase, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Suppression, Genetic, beta-Galactosidase
Genetics
Date: Mar. 01, 1999
PubMed ID: 10049917
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