ERp18 regulates activation of ATF6α during unfolded protein response.
Ojore Benedict Valentine OkaMarcel van LithJana RudolfWanida TungkumMarie Anne PringleNeil John BulleidPublished in: The EMBO journal (2019)
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.
Keyphrases
- transcription factor
- endoplasmic reticulum stress
- endoplasmic reticulum
- induced apoptosis
- dna binding
- genome wide identification
- quality control
- estrogen receptor
- gene expression
- breast cancer cells
- small molecule
- oxidative stress
- cell proliferation
- epithelial mesenchymal transition
- genome wide
- protein protein
- copy number
- hepatitis c virus
- binding protein
- cell cycle arrest
- antiretroviral therapy