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. 2023 Feb 15;15:1047897. doi: 10.3389/fnagi.2023.1047897

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Copyright © 2023 Jeon, Kwon, Lee and Kim.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Unfolded protein response (UPR) pathway. In normal condition, GRP78/BiP interact with UPR sensors (PERK, ATF6, and IRE1). When misfolded or unfolded proteins accumulated in ER, GRP78/BiP dissociated from UPR sensors and can bind to misfolded or unfolded proteins. (1) Protein kinase RNA-like endoplasmic reticulum kinase (PERK) autophosphorylates and induces eIF2α phosphorylation. (2) Activating transcription Factor 6 (ATF6) moves into Golgi apparatus and cleaved by S1P and S2P. Cleaved ATF6 moves into nucleus, activates UPR genes. (3) IRE1 autophosphorylates and splices XBP1.