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

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.
Mesh Terms:
Cell Cycle Proteins, Cluster Analysis, F-Box Proteins, GTP-Binding Protein alpha Subunits, Gq-G11, GTP-Binding Protein beta Subunits, GTP-Binding Proteins, Gene Expression Profiling, Gene Expression Regulation, Fungal, Genome, Fungal, Humans, Phenotype, Pheromones, Promoter Regions, Genetic, Recombinant Fusion Proteins, Reproducibility of Results, SKP Cullin F-Box Protein Ligases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Substrate Specificity, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases
Mol. Cell
Date: Jun. 11, 2010
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