IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
Howard Hughes Medical Institute · University of Alberta · +3 more institutions
Abstract
All eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded protein response (UPR). In yeast, a type-I ER transmembrane protein kinase, Ire1p, is the proximal sensor of unfolded proteins in the ER lumen that initiates an unconventional splicing reaction on HAC1 mRNA. Hac1p is a transcription factor required for induction of UPR genes. In higher eukaryotic cells, the UPR also induces site-2 protease (S2P)-mediated cleavage of ER-localized ATF6 to generate an N-terminal fragment that activates transcription of UPR genes. To elucidate the requirements for IRE1alpha and ATF6 for signaling the mammalian UPR, we…
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Authors
9- KLKyung‐Ho LeeCorresponding
Howard Hughes Medical Institute, University of Alberta, Kyoto University, University of Michigan, Columbia University
- WTWitoon Tirasophon
Howard Hughes Medical Institute, University of Alberta, Kyoto University, University of Michigan, Columbia University
- XSXiaohua Shen
Howard Hughes Medical Institute, University of Alberta, Kyoto University, University of Michigan, Columbia University
- MMMarek Michalak
Howard Hughes Medical Institute, University of Alberta, Kyoto University, University of Michigan, Columbia University
- RPRon Prywes
Howard Hughes Medical Institute, University of Alberta, Kyoto University, University of Michigan, Columbia University
Topics & keywords
- XBP1
- Unfolded protein response
- Biology
- Endoplasmic reticulum
- Cell biology
- ATF6
- RNA splicing
- Molecular biology