Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum
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Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. / Jonikas, Martin C; Collins, Sean R; Denic, Vladimir; Oh, Eugene; Quan, Erin M; Schmid, Volker; Weibezahn, Jimena; Schwappach, Blanche; Walter, Peter; Weissman, Jonathan S; Schuldiner, Maya.
in: SCIENCE, Jahrgang 323, Nr. 5922, 27.03.2009, S. 1693-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum
AU - Jonikas, Martin C
AU - Collins, Sean R
AU - Denic, Vladimir
AU - Oh, Eugene
AU - Quan, Erin M
AU - Schmid, Volker
AU - Weibezahn, Jimena
AU - Schwappach, Blanche
AU - Walter, Peter
AU - Weissman, Jonathan S
AU - Schuldiner, Maya
PY - 2009/3/27
Y1 - 2009/3/27
N2 - Protein folding in the endoplasmic reticulum is a complex process whose malfunction is implicated in disease and aging. By using the cell's endogenous sensor (the unfolded protein response), we identified several hundred yeast genes with roles in endoplasmic reticulum folding and systematically characterized their functional interdependencies by measuring unfolded protein response levels in double mutants. This strategy revealed multiple conserved factors critical for endoplasmic reticulum folding, including an intimate dependence on the later secretory pathway, a previously uncharacterized six-protein transmembrane complex, and a co-chaperone complex that delivers tail-anchored proteins to their membrane insertion machinery. The use of a quantitative reporter in a comprehensive screen followed by systematic analysis of genetic dependencies should be broadly applicable to functional dissection of complex cellular processes from yeast to human.
AB - Protein folding in the endoplasmic reticulum is a complex process whose malfunction is implicated in disease and aging. By using the cell's endogenous sensor (the unfolded protein response), we identified several hundred yeast genes with roles in endoplasmic reticulum folding and systematically characterized their functional interdependencies by measuring unfolded protein response levels in double mutants. This strategy revealed multiple conserved factors critical for endoplasmic reticulum folding, including an intimate dependence on the later secretory pathway, a previously uncharacterized six-protein transmembrane complex, and a co-chaperone complex that delivers tail-anchored proteins to their membrane insertion machinery. The use of a quantitative reporter in a comprehensive screen followed by systematic analysis of genetic dependencies should be broadly applicable to functional dissection of complex cellular processes from yeast to human.
KW - Endoplasmic Reticulum/metabolism
KW - Epistasis, Genetic
KW - Gene Deletion
KW - Gene Expression Regulation, Fungal
KW - Genes, Fungal
KW - Genes, Reporter
KW - Membrane Proteins/chemistry
KW - Mutation
KW - Phenotype
KW - Protein Folding
KW - Protein Processing, Post-Translational
KW - Protein Structure, Tertiary
KW - Saccharomyces cerevisiae/genetics
KW - Saccharomyces cerevisiae Proteins/chemistry
KW - Secretory Pathway
U2 - 10.1126/science.1167983
DO - 10.1126/science.1167983
M3 - SCORING: Journal article
C2 - 19325107
VL - 323
SP - 1693
EP - 1697
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 5922
ER -