ERp18 regulates activation of ATF6α during unfolded protein response.

The EMBO Journal
Ojore Bv OkaNeil J Bulleid

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.

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Citations

Nov 15, 2019·F1000Research·G Elif KaragözDiego Acosta-Alvear
Sep 6, 2020·The Journal of Biological Chemistry·Julia M D Grandjean, R Luke Wiseman
Sep 12, 2020·American Journal of Respiratory Cell and Molecular Biology·Sanaz DastghaibAmir A Zeki
Apr 7, 2020·Redox Biology·Yvonne Janssen-HeiningerVikas Anathy
Nov 23, 2019·Trends in Biochemical Sciences·Noelia Pastor-CantizanoFederica Brandizzi
Mar 20, 2021·Journal of Molecular Neuroscience : MN·Liang HanYuxiu Shi
Mar 30, 2021·Cell Structure and Function·Quynh Giang Le, Yukio Kimata
Aug 10, 2021·Immunological Reviews·Daniela RicciYair Argon

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Methods Mentioned

BETA
glycosylation
PCR
transfection

Software Mentioned

Cor Image Studio
Li
GenScript
PeakView
Origin
Mascot

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