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Mol Cell

Title:		Systematic analysis of essential genes reveals important regulators of G protein signaling
Author(s):		Cappell SD; Baker R; Skowyra D; Dohlman HG;
Address:		"Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"
Journal Title:		Mol Cell
Year:		2010
Volume:		38
Issue:		5
Page Number:		746 - 757
DOI:		10.1016/j.molcel.2010.05.026
ISSN/ISBN:		1097-4164 (Electronic) 1097-2765 (Print) 1097-2765 (Linking)
Abstract:		"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"
Keywords:		"Anaphase-Promoting Complex-Cyclosome Cell Cycle Proteins/genetics/metabolism Cluster Analysis F-Box Proteins/genetics/metabolism GTP-Binding Protein alpha Subunits, Gq-G11/genetics/metabolism GTP-Binding Protein beta Subunits/genetics/metabolism GTP-Bindi;"
Notes:		"MedlineCappell, Steven D Baker, Rachael Skowyra, Dorota Dohlman, Henrik G eng R01 GM059167/GM/NIGMS NIH HHS/ R01 GM059167-12/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2010/06/15 Mol Cell. 2010 Jun 11; 38(5):746-57. doi: 10.1016/j.molcel.2010.05.026"