Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development

Cell. 2001 Dec 28;107(7):893-903. doi: 10.1016/s0092-8674(01)00612-2.

Abstract

The unfolded protein response (UPR) is a transcriptional and translational intracellular signaling pathway activated by the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). We have used C. elegans as a genetic model system to dissect UPR signaling in a multicellular organism. C. elegans requires ire-1-mediated splicing of xbp-1 mRNA for UPR gene transcription and survival upon ER stress. In addition, ire-1/xbp-1 acts with pek-1, a protein kinase that mediates translation attenuation, in complementary pathways that are essential for worm development and survival. We propose that UPR transcriptional activation by ire-1 as well as translational attenuation by pek-1 maintain ER homeostasis. The results demonstrate that the UPR and ER homeostasis are essential for metazoan development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins*
  • Fungal Proteins / genetics
  • MAP Kinase Kinase 1*
  • Membrane Glycoproteins / genetics
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Molecular Sequence Data
  • Mutation
  • Protein Folding*
  • Protein-Serine-Threonine Kinases*
  • Repressor Proteins / genetics
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcriptional Activation / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Fungal Proteins
  • Membrane Glycoproteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • XBP1 protein, S cerevisiae
  • IRE1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • pek-1 protein, C elegans
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase Kinases