BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha.

Details

Serval ID
serval:BIB_B63C0573C930
Type
Article: article from journal or magazin.
Collection
Publications
Title
BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha.
Journal
Molecular Cell
Author(s)
Lisbona F., Rojas-Rivera D., Thielen P., Zamorano S., Todd D., Martinon F., Glavic A., Kress C., Lin J.H., Walter P., Reed J.C., Glimcher L.H., Hetz C.
ISSN
1097-4164 (Electronic)
ISSN-L
1097-2765
Publication state
Published
Issued date
2009
Volume
33
Number
6
Pages
679-691
Language
english
Abstract
Adaptation to endoplasmic reticulum (ER) stress depends on the activation of an integrated signal transduction pathway known as the unfolded protein response (UPR). Bax inhibitor-1 (BI-1) is an evolutionarily conserved ER-resident protein that suppresses cell death. Here we have investigated the role of BI-1 in the UPR. BI-1 expression suppressed IRE1alpha activity in fly and mouse models of ER stress. BI-1-deficient cells displayed hyperactivation of the ER stress sensor IRE1alpha, leading to increased levels of its downstream target X-box-binding protein-1 (XBP-1) and upregulation of UPR target genes. This phenotype was associated with the formation of a stable protein complex between BI-1 and IRE1alpha, decreasing its ribonuclease activity. Finally, BI-1 deficiency increased the secretory activity of primary B cells, a phenomenon regulated by XBP-1. Our results suggest a role for BI-1 in early adaptive responses against ER stress that contrasts with its known downstream function in apoptosis.
Keywords
Amino Acid Sequence, Animals, Apoptosis/physiology, Apoptosis Regulatory Proteins/genetics, Apoptosis Regulatory Proteins/metabolism, B-Lymphocytes/metabolism, Cells, Cultured, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/metabolism, Endoplasmic Reticulum/physiology, Endoribonucleases/genetics, Endoribonucleases/metabolism, Fibroblasts/cytology, Fibroblasts/metabolism, Humans, Immunoglobulin M/metabolism, Membrane Proteins/genetics, Membrane Proteins/metabolism, Mice, Mice, Knockout, Molecular Sequence Data, Protein-Serine-Threonine Kinases/genetics, Protein-Serine-Threonine Kinases/metabolism, RNA Splicing, Sequence Homology, Amino Acid, Transcription Factors/genetics, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
21/02/2011 15:36
Last modification date
20/08/2019 15:24
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