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The Luminal Domain of ATF6 Senses Endoplasmic Reticulum (ER) Stress and Causes Translocation of ATF6 from the ER to the Golgi
Open accessAbstract
ATF6 is an endoplasmic reticulum (ER) transmembrane transcription factor that is activated by the ER stress/unfolded protein response by cleavage of its N-terminal half from the membrane. We find that ER stress induces ATF6 to move from the ER to the Golgi, where it is cut in its luminal domain by site 1 protease. ATF6 contains a single transmembrane domain with 272 amino acids oriented in the lumen of the ER. We found that this luminal domain is required for the translocation of ATF6 to the Golgi and its subsequent cleavage, and we have mapped regions required for these properties. These results suggest that the conserved CD1 region is required for translocation, whereas the CD2 region is required for site 1 protease cleavage. We also find that ATF6's luminal domain is sufficient to sense ER stress and cause translocation to the Golgi when fused to LZIP, another ER transmembrane protein. These results show that ATF6 has a mechanism to sense ER stress and respond by translocation to the Golgi.
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Citations
Cites
ER Stress Induces Cleavage of Membrane-Bound ATF6 by the Same Proteases that Process SREBPs
Ye, J., Rawson, R. B., Komuro, R., Chen, X., Davé, U. P., Prywes, R., Brown, M. S., & Goldstein, J. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00133-7 · Cited by 1,871
Self-citationYoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., Negishi, M., & Mori, K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6755-6767.2000 · Cited by 934
Cited by
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802
Shen, J., Chen, X., Hendershot, L., & Prywes, R. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00203-4 · Cited by 1,456
Self-citationYoshida, H. (2007) · The FEBS Journal · doi:10.1111/j.1742-4658.2007.05639.x · Cited by 1,086
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044
The endoplasmic reticulum stress response in immunity and autoimmunity
Todd, D. J., Lee, A.-H., & Glimcher, L. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2359 · Cited by 623
Metadata
- Authors
- Chen, X., Shen, J., & Prywes, R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 277
- Issue
- 15
- Pages
- 13045-13052
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2122647692
- Cited by
- 488
- References
- 2
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Chen, X., Shen, J., & Prywes, R. (2002). The Luminal Domain of ATF6 Senses Endoplasmic Reticulum (ER) Stress and Causes Translocation of ATF6 from the ER to the Golgi. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110636200
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