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

doi:10.1016/S0092-8674(01)00612-2

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

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423 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 language	English (US)
Pages (from-to)	893-903
Number of pages	11
Journal	Cell
Volume	107
Issue number	7
DOIs	https://doi.org/10.1016/S0092-8674(01)00612-2
State	Published - Dec 28 2001
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/S0092-8674(01)00612-2

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

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.",

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

note = "Funding Information: We thank the C. elegans Gene Knockout Consortium (Oklahoma) for isolation of pek-1(ok275) deletion allele. We thank the Caenorhabditis Genetics Center for strains. We thank previous and current members of the Ellis laboratory and members of the Kaufman laboratory for assistance provided throughout this study. This work was supported in part by NIH grant 5RO1 AI-42394-04 (R.J.K.).",

year = "2001",

month = dec,

day = "28",

doi = "10.1016/S0092-8674(01)00612-2",

language = "English (US)",

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pages = "893--903",

journal = "Cell",

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TY - JOUR

T1 - Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development

AU - Shen, Xiaohua

AU - Ellis, Ronald E.

AU - Lee, Kyungho

AU - Liu, Chuan Yin

AU - Yang, Kun

AU - Solomon, Aaron

AU - Yoshida, Hiderou

AU - Morimoto, Rick

AU - Kurnit, David M.

AU - Mori, Kazutoshi

AU - Kaufman, Randal J.

N1 - Funding Information: We thank the C. elegans Gene Knockout Consortium (Oklahoma) for isolation of pek-1(ok275) deletion allele. We thank the Caenorhabditis Genetics Center for strains. We thank previous and current members of the Ellis laboratory and members of the Kaufman laboratory for assistance provided throughout this study. This work was supported in part by NIH grant 5RO1 AI-42394-04 (R.J.K.).

PY - 2001/12/28

Y1 - 2001/12/28

N2 - 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.

AB - 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.

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SN - 0092-8674

VL - 107

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EP - 903

JO - Cell

JF - Cell

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ER -

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

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