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

Xiaohua Shen, Ronald E. Ellis, Kyungho Lee, Chuan Yin Liu, Kun Yang, Aaron Solomon, Hiderou Yoshida, Rick Morimoto, David M. Kurnit, Kazutoshi Mori, Randal J. Kaufman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

480 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)893-903
Number of pages11
JournalCell
Volume107
Issue number7
DOIs
StatePublished - Dec 28 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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