The Unfolded Protein Response Supports Cellular Robustness as a Broad-Spectrum Compensatory Pathway

Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20597-602. doi: 10.1073/pnas.1117184109. Epub 2011 Dec 5.

Abstract

Stress pathways monitor intracellular systems and deploy a range of regulatory mechanisms in response to stress. One of the best-characterized pathways, the unfolded protein response (UPR), is responsible for maintaining endoplasmic reticulum (ER) homeostasis. The highly conserved Ire1 branch regulates hundreds of gene targets by activating a UPR-specific transcription factor. To understand how the UPR manages ER stress, a unique genetic approach was applied to reveal how the system corrects disequilibria. The data show that the UPR can address a wide range of dysfunctions that are otherwise lethal if not for its intervention. Transcriptional profiling of stress-alleviated cells shows that the program can be modulated, not just in signal amplitude, but also through differential target gene expression depending on the stress. The breadth of the functions mitigated by the UPR further supports its role as a major mechanism maintaining systems robustness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Endoplasmic Reticulum / metabolism
  • Fungal Proteins / chemistry*
  • Gene Deletion
  • Glycosylation
  • Models, Genetic
  • Molecular Conformation
  • Mutation
  • Phenotype
  • Protein Denaturation
  • Protein Folding
  • Signal Transduction
  • Temperature
  • Transcription, Genetic
  • Unfolded Protein Response*
  • beta-Galactosidase / metabolism

Substances

  • Fungal Proteins
  • beta-Galactosidase

Associated data

  • GEO/GSE33844