The Bcl-2 family protein bid interacts with the ER stress sensor IRE1 to differentially modulate its RNase activity

Bashir, S and Banday, M and Qadri, O and Pal, D and Bashir, A and Hilal, N and Altaf, M and Fazili, KM (2023) The Bcl-2 family protein bid interacts with the ER stress sensor IRE1 to differentially modulate its RNase activity. In: FEBS Letters .

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Abstract

IRE1 is a transmembrane signalling protein that activates the unfolded protein response under endoplasmic reticulum stress. IRE1 is endowed with kinase and endoribonuclease activities. The ribonuclease activity of IRE1 can switch substrate specificities to carry out atypical splicing of Xbp1 mRNA or trigger the degradation of specific mRNAs. The mechanisms regulating the distinct ribonuclease activities of IRE1 have yet to be fully understood. Here, we report the Bcl-2 family protein Bid as a novel recruit of the IRE1 complex, which directly interacts with the cytoplasmic domain of IRE1. Bid binding to IRE1 leads to a decrease in IRE1 phosphorylation in a way that it can only perform Xbp1 splicing while mRNA degradation activity is repressed. The RNase outputs of IRE1 have been found to regulate the homeostatic–apoptotic switch. This study, thus, provides insight into IRE1-mediated cell survival. © 2023 Federation of European Biochemical Societies.

Item Type:	Journal Article
Publication:	FEBS Letters
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright of this article belongs to John Wiley and Sons Inc.
Keywords:	Bid; IRE1; phosphorylation; RNase activity; UPRosome
Department/Centre:	Division of Interdisciplinary Sciences > Computational and Data Sciences
Date Deposited:	10 Mar 2023 10:28
Last Modified:	10 Mar 2023 10:28
URI:	https://eprints.iisc.ac.in/id/eprint/80949

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