Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development.
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.
Shen
X
X
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ellis
R E
RE
Lee
K
K
Liu
C Y
CY
Yang
K
K
Solomon
A
A
Yoshida
H
H
Morimoto
R
R
Kurnit
D M
DM
Mori
K
K
Kaufman
R J
RJ
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins / Q000235:genetics; D048369:MAP Kinase Kinase 1; D008562:Membrane Glycoproteins / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C108767:XBP1 protein, S cerevisiae; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C499574:pek-1 protein, C elegans; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases