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ER p18 regulates activation of ATF 6α during unfolded protein response
Author(s) -
Oka Ojore BV,
Lith Marcel,
Rudolf Jana,
Tungkum Wanida,
Pringle Marie Anne,
Bulleid Neil J
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100990
Subject(s) - golgi apparatus , atf6 , unfolded protein response , microbiology and biotechnology , endoplasmic reticulum , activating transcription factor , transcription factor , proteolysis , biology , chemistry , biochemistry , gene , enzyme
Activation of the ATF 6α signaling pathway is initiated by trafficking of ATF 6α 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 ATF 6α are regulated and whether additional protein partners are required for its localization and processing remain unresolved. Here, we show that ER ‐resident oxidoreductase ER p18 associates with ATF 6α following ER stress and plays a key role in both trafficking and activation of ATF 6α. We find that ER p18 depletion attenuates the ATF 6α stress response. Paradoxically, ER stress accelerates trafficking of ATF 6α to the Golgi in ER p18‐depleted cells. However, the translocated ATF 6α becomes aberrantly processed preventing release of the soluble transcription factor. Hence, we demonstrate that ER p18 monitors ATF 6α ER quality control to ensure optimal processing following trafficking to the Golgi.