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. 2019 Nov 19;10:748. doi: 10.3389/fendo.2019.00748

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Copyright © 2019 Teeli, Leszczyński, Krishnaswamy, Ogawa, Tsuchiya, Śmiech, Skarzynski and Taniguchi.

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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Molecular mechanism of UPR. ER Stress-activated three pathways (IRE, PERK, and ATF6) control the activity of XBP1s, ATF4, ATF6 transcription factors and regulate UPR related gene expressions, which triggers autophagy. On the other hand, Beclin1 forms a complex with PI3KIII and p150, and this also triggers autophagy mechanism. In Caenorhabditis elegans, SKN-1, the ortholog of human Nrf1-3, has been reported to regulate ATF6 and XBP1 expressions at the promoter level. ER, endoplasmic reticulum; GRP78, Glucose-regulated protein; PERK, PKR-like eukaryotic initiation factor 2α (eIF2α) kinase; IRE1, inositol-requiring transmembrane kinase/endoribonuclease 1; ATF6, activating transcription factor-6; XBP1, X-box-binding protein 1; XBP1s, spliced XBP1 protein; S1P and S2P, site-1 and site-2 proteases; PI3KIII, Class III PI 3-kinase; Skn1, Protein skinhead-1.