BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha
- PMID: 19328063
- PMCID: PMC2818874
- DOI: 10.1016/j.molcel.2009.02.017
BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha
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.
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Comment in
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Intricate links between ER stress and apoptosis.Mol Cell. 2009 Mar 27;33(6):669-70. doi: 10.1016/j.molcel.2009.03.002. Mol Cell. 2009. PMID: 19328058
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