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Role of Disulfide Bridges Formed in the Luminal Domain of ATF6 in Sensing Endoplasmic Reticulum Stress

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Nadanaka, Satomi, Okada, Tetsuya, Yoshida, Hiderou, Mori, Kazutoshi·2007·Molecular and Cellular Biology

Abstract

ATF6 is a membrane-bound transcription factor activated by proteolysis in response to endoplasmic reticulum (ER) stress to induce the transcription of ER chaperone genes. We show here that, owing to the presence of intra- and intermolecular disulfide bridges formed between the two conserved cysteine residues in the luminal domain, ATF6 occurs in unstressed ER in monomer, dimer, and oligomer forms. Disulfide-bonded ATF6 is reduced upon treatment of cells with not only the reducing reagent dithiothreitol but also the glycosylation inhibitor tunicamycin, and the extent of reduction correlates with that of activation. Although reduction is not sufficient for activation, fractionation studies show that only reduced monomer ATF6 reaches the Golgi apparatus, where it is cleaved by the sequential action of the two proteases S1P and S2P. Reduced monomer ATF6 is found to be a better substrate than disulfide-bonded forms for S1P. ER stress-induced reduction is specific to ATF6 as the oligomeric status of a second ER membrane-bound transcription factor, LZIP/Luman, is not changed upon tunicamycin treatment and LZIP/Luman is well cleaved by S1P in the absence of ER stress. This mechanism ensures the strictness of regulation, in that the cell can only process ATF6 which has experienced the changes in the ER.

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Metadata

Authors
Nadanaka, S., Okada, T., Yoshida, H., & Mori, K.
Venue
Molecular and Cellular Biology
Published
2007-02-01
Volume
27
Issue
3
Pages
1027-1043
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2164783065
Cited by
266
References
50
FWCI
3.87
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Role of Disulfide Bridges Formed in the Luminal Domain of ATF6 in Sensing Endoplasmic Reticulum Stress. https://app.cochat.ai/papers/10.1128/mcb.00408-06
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Nadanaka, S., Okada, T., Yoshida, H., & Mori, K. (2007). Role of Disulfide Bridges Formed in the Luminal Domain of ATF6 in Sensing Endoplasmic Reticulum Stress. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.00408-06

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