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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins
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Cell Cycle Proteins*
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Fungal Proteins / genetics
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MAP Kinase Kinase 1*
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Membrane Glycoproteins / genetics
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Mitogen-Activated Protein Kinase Kinases / genetics
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Molecular Sequence Data
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Mutation
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Protein Folding*
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Protein Serine-Threonine Kinases*
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Repressor Proteins / genetics
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Saccharomyces cerevisiae Proteins*
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Signal Transduction*
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Transcription Factors / genetics
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Transcriptional Activation / physiology*
Substances
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Caenorhabditis elegans Proteins
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Cell Cycle Proteins
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Fungal Proteins
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Membrane Glycoproteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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XBP1 protein, S cerevisiae
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IRE1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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pek-1 protein, C elegans
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MAP Kinase Kinase 1
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Mitogen-Activated Protein Kinase Kinases