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Peer review Peer review information Nature Health thanks Anand Krishnan, Andrea Schaffer and the other, anonymous, reviewer(s) for their contribution to the peer review of this work

2.1 UPR signaling pathways 2.1.1 IRE1-dependent unfolded protein response signaling pathway Inositol-requiring enzyme 1, a type-I transmembrane protein involved in multiple cellular processes, has a serine/threonine kinase domain and an endoribonuclease (RNase) domain in C-terminal cytoplasmic region and an ER luminal domain in N-terminal [21, 22]

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