| Autor: |
Valentine Oka, Ojore Benedict, Pierre, Arvin Shedrach, Pringle, Marie Anne, Tungkum, Wanida, Cao, Zhenbo, Fleming, Bethany, Bulleid, Neil John |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/22/2022, Vol. 119 Issue 12, p1-11, 11p |
| Abstrakt: |
The unfolded protein response (UPR) maintains cellular proteostasis during stress by activating sensors located to the endoplasmic reticulum (ER) membrane. A major sensor for this response, ATF6α, is activated by release from ER retention and trafficking to the Golgi, where it is cleaved to generate a bZIP transactivator to initiate a transcriptional response. The reduction of a disulfide in monomeric ATF6α is thought to be necessary for release from retention, trafficking, and proteolysis. Here we show that, following ER stress, ATF6α undergoes a redox switch to form a disulfide bonded dimer, which traffics to the Golgi for cleavage by the S1P protease. Additionally, we find that overexpression of ERp18 attenuates dimer formation thereby limiting Golgi trafficking. Our results provide mechanistic insight into activation of the ATF6α pathway, revealing an unexpected role for redox-dependent oligomerization prior to Golgi trafficking. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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