Fus3p and Kss1p control G1 arrest in Saccharomyces cerevisiae through a balance of distinct arrest and proliferative functions that operate in parallel with Far1p

Genetics. 1999 Mar;151(3):989-1004. doi: 10.1093/genetics/151.3.989.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aspartic Acid Endopeptidases*
  • Blotting, Northern
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics*
  • Cell Cycle / genetics*
  • Cell Cycle Proteins*
  • Crosses, Genetic
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins / genetics*
  • Cytoskeletal Proteins / genetics
  • Dose-Response Relationship, Drug
  • Fungal Proteins / genetics*
  • Fungal Proteins / physiology*
  • G1 Phase / genetics
  • Gene Expression
  • Gene Expression Regulation, Fungal
  • Genotype
  • Immunoblotting
  • Mating Factor
  • Mitogen-Activated Protein Kinases*
  • Models, Biological
  • Peptides / pharmacology
  • Repressor Proteins*
  • S Phase / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins*
  • Suppression, Genetic
  • beta-Galactosidase / genetics

Substances

  • CLN2 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins
  • Cytoskeletal Proteins
  • FAR1 protein, S cerevisiae
  • Fungal Proteins
  • Peptides
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Mating Factor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • FUS3 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases
  • beta-Galactosidase
  • Aspartic Acid Endopeptidases
  • BAR1 protein, S cerevisiae