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. 2023 Apr;597(7):962-974.
doi: 10.1002/1873-3468.14593. Epub 2023 Feb 16.

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

Samirul Bashir  1 , Mariam Banday  1 , Ozaira Qadri  1 , Debnath Pal  2 , Arif Bashir  1 , Nazia Hilal  1 , Mohammad Altaf  1 , Khalid Majid Fazili  1
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Free article

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

Samirul Bashir et al. FEBS Lett. 2023 Apr.
Free article

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.

Keywords: Bid; IRE1; RNase activity; UPRosome; phosphorylation.

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