Oka, O. B.V. , van Lith, M., Rudolf, J., Tungkum, W., Pringle, M.-A. and Bulleid, N. J. (2019) ERp18 regulates the activation of ATF6α during the unfolded protein response. EMBO Journal, 2019, e100990. (doi: 10.15252/embj.2018100990) (PMID:31209066)
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Abstract
Activation of the ATF6α signaling pathway is initiated by trafficking of ATF6α from the ER to the Golgi apparatus. Its subsequent proteolysis releases a transcription factor that translocates to the nucleus causing downstream gene activation. How ER retention, Golgi trafficking, and proteolysis of ATF6α are regulated and whether additional protein partners are required for its localization and processing remain unresolved. Here, we show that ER‐resident oxidoreductase ERp18 associates with ATF6α following ER stress and plays a key role in both trafficking and activation of ATF6α. We find that ERp18 depletion attenuates the ATF6α stress response. Paradoxically, ER stress accelerates trafficking of ATF6α to the Golgi in ERp18‐depleted cells. However, the translocated ATF6α becomes aberrantly processed preventing release of the soluble transcription factor. Hence, we demonstrate that ERp18 monitors ATF6α ER quality control to ensure optimal processing following trafficking to the Golgi.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Van Lith, Dr Marcel and Rudolf, Dr Jana and Bulleid, Professor Neil and Pringle, Mrs Marie and Tungkum, Wanida and Oka, Dr Ojore |
| Authors: | Oka, O. B.V., van Lith, M., Rudolf, J., Tungkum, W., Pringle, M.-A., and Bulleid, N. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | EMBO Journal |
| Publisher: | EMBO Press |
| ISSN: | 0261-4189 |
| ISSN (Online): | 1460-2075 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in EMBO Journal 2019:e100990 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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