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Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum.

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.

Pubmed ID: 19325107


  • Jonikas MC
  • Collins SR
  • Denic V
  • Oh E
  • Quan EM
  • Schmid V
  • Weibezahn J
  • Schwappach B
  • Walter P
  • Weissman JS
  • Schuldiner M


Science (New York, N.Y.)

Publication Data

March 27, 2009

Associated Grants

  • Agency: Wellcome Trust, Id: 081671
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Endoplasmic Reticulum
  • Epistasis, Genetic
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Genes, Reporter
  • Membrane Proteins
  • Mutation
  • Phenotype
  • Protein Folding
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Secretory Pathway