Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast

Cell. 2004 Dec 29;119(7):991-1000. doi: 10.1016/j.cell.2004.11.052.

Abstract

The yeast MAPK pathways required for mating versus filamentous growth share multiple components yet specify distinct programs. The mating-specific MAPK, Fus3, prevents crosstalk between the two pathways by unknown mechanisms. Here we show that pheromone signaling induces Fus3-dependent degradation of Tec1, the transcription factor specific to the filamentation pathway. Degradation requires Fus3 kinase activity and a MAPK phosphorylation site in Tec1 at threonine 273. Fus3 associates with Tec1 in unstimulated cells, and active Fus3 phosphorylates Tec1 on T273 in vitro. Destruction of Tec1 requires the F box protein Dia2 (Digs-into-agar-2), and Cdc53, the Cullin of SCF (Skp1-Cdc53-F box) ubiquitin ligases. Notably, mutation of the phosphoacceptor site in Tec1, deletion of FUS3, or deletion of DIA2 results in a loss of signaling specificity such that pheromone pathway signaling erroneously activates filamentation pathway gene expression and invasive growth. Signal-induced destruction of a transcription factor for a competing pathway provides a mechanism for signaling specificity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • MAP Kinase Signaling System / drug effects*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Mutation
  • Pheromones / pharmacology*
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • SKP Cullin F-Box Protein Ligases / deficiency
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Substrate Specificity
  • Threonine / genetics
  • Threonine / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism

Substances

  • Cdc53 protein, S cerevisiae
  • Cell Cycle Proteins
  • Cullin Proteins
  • DNA-Binding Proteins
  • Dia2 protein, S cerevisiae
  • F-Box Proteins
  • Pheromones
  • Saccharomyces cerevisiae Proteins
  • TEC1 protein, S cerevisiae
  • Transcription Factors
  • Ubiquitin
  • Threonine
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • SKP Cullin F-Box Protein Ligases
  • FUS3 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases