Systematic analysis of essential genes reveals important regulators of G protein signaling

Mol Cell. 2010 Jun 11;38(5):746-57. doi: 10.1016/j.molcel.2010.05.026.


The yeast pheromone pathway consists of a canonical heterotrimeric G protein and MAP kinase cascade. To identify additional signaling components, we systematically evaluated 870 essential genes using a library of repressible-promoter strains. Quantitative transcription-reporter and MAPK activity assays were used to identify strains that exhibit altered pheromone sensitivity. Of the 92 newly identified essential genes required for proper G protein signaling, those involved with protein degradation were most highly represented. Included in this group are members of the Skp, Cullin, F box (SCF) ubiquitin ligase complex. Further genetic and biochemical analysis reveals that SCF(Cdc4) acts together with the Cdc34 ubiquitin-conjugating enzyme at the level of the G protein; promotes degradation of the G protein alpha subunit, Gpa1, in vivo; and catalyzes Gpa1 ubiquitination in vitro. These insights to the G protein signaling network reveal the essential genome as an untapped resource for identifying new components and regulators of signal transduction pathways.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cluster Analysis
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • GTP-Binding Protein beta Subunits / genetics
  • GTP-Binding Protein beta Subunits / metabolism
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Genome, Fungal
  • Humans
  • Phenotype
  • Pheromones / genetics
  • Pheromones / metabolism
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Reproducibility of Results
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / genetics*
  • Substrate Specificity
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligase Complexes / genetics
  • Ubiquitin-Protein Ligase Complexes / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism


  • CDC4 protein, S cerevisiae
  • Cell Cycle Proteins
  • F-Box Proteins
  • GTP-Binding Protein beta Subunits
  • Pheromones
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Ste4 protein, S cerevisiae
  • CDC34 protein, S cerevisiae
  • CDC34 protein, human
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases
  • GTP-Binding Proteins
  • GPA1 protein, S cerevisiae
  • GTP-Binding Protein alpha Subunits, Gq-G11