Fus3-regulated Tec1 Degradation Through SCFCdc4 Determines MAPK Signaling Specificity During Mating in Yeast

Cell. 2004 Dec 29;119(7):981-90. doi: 10.1016/j.cell.2004.11.053.

Abstract

Signaling specificity is fundamental for parallel mitogen-activated protein kinase (MAPK) cascades that control growth and differentiation in response to different stimuli. In Saccharomyces cerevisiae, components of the pheromone-responsive MAPK cascade activate Fus3 and Kss1 MAPKs to induce mating and Kss1 to promote filamentation. Active Fus3 is required to prevent the activation of the filamentation program during pheromone response. How Fus3 prevents the crossactivation is not clear. Here we show that Tec1, a cofactor of Ste12 for the expression of filamentation genes, is rapidly degraded during pheromone response. Fus3 but not Kss1 induces Tec1 ubiquination and degradation through the SCFCdc4 ubiquitin ligase. T273 in a predicted high-affinity Cdc4 binding motif is phosphorylated by Fus3 both in vitro and in vivo. Tec1T273V blocks Tec1 ubiquitination and degradation and allows the induction of filamentation genes in response to pheromone. Thus, Fus3 inhibits filamentous growth during mating by degrading Tec1.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • MAP Kinase Signaling System* / drug effects
  • Mating Factor
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutation
  • Peptides / pharmacology*
  • Pheromones / pharmacology*
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Threonine / genetics
  • Threonine / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / drug effects
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • CDC4 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • F-Box Proteins
  • Peptides
  • Pheromones
  • Saccharomyces cerevisiae Proteins
  • TEC1 protein, S cerevisiae
  • Transcription Factors
  • Ubiquitin
  • Threonine
  • Mating Factor
  • Ubiquitin-Protein Ligases
  • FUS3 protein, S cerevisiae
  • KSS1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases