Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1 - PubMed (original) (raw)
Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1
Keisuke Yamamoto et al. Dev Cell. 2007 Sep.
Free article
Abstract
Metazoans express three unfolded protein response transducers (IRE1, PERK, and ATF6) ubiquitously to cope with endoplasmic reticulum (ER) stress. ATF6 is an ER membrane-bound transcription factor activated by ER stress-induced proteolysis and has been duplicated in mammals. Here, we generated ATF6alpha- and ATF6beta-knockout mice, which developed normally, and then found that their double knockout caused embryonic lethality. Analysis of mouse embryonic fibroblasts (MEFs) deficient in ATF6alpha or ATF6beta revealed that ATF6alpha is solely responsible for transcriptional induction of ER chaperones and that ATF6alpha heterodimerizes with XBP1 for the induction of ER-associated degradation components. ATF6alpha(-/-) MEFs are sensitive to ER stress. Unaltered responses observed in ATF6beta(-/-) MEFs indicate that ATF6beta is not a negative regulator of ATF6alpha. These results demonstrate that ATF6alpha functions as a critical regulator of ER quality control proteins in mammalian cells, in marked contrast to worm and fly cells in which IRE1 is responsible.
Comment in
- Coping with stress: ATF6alpha takes the stage.
Bobrovnikova-Marjon E, Diehl JA. Bobrovnikova-Marjon E, et al. Dev Cell. 2007 Sep;13(3):322-4. doi: 10.1016/j.devcel.2007.08.006. Dev Cell. 2007. PMID: 17765676
Similar articles
- Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 and IRE1/XBP1 arms of the pathway.
Gjymishka A, Su N, Kilberg MS. Gjymishka A, et al. Biochem J. 2009 Feb 1;417(3):695-703. doi: 10.1042/BJ20081706. Biochem J. 2009. PMID: 18840095 Free PMC article. - Partial limitation of cellular functions and compensatory modulation of unfolded protein response pathways caused by double-knockout of ATF6α and ATF6β.
Akai R, Hamashima H, Saito M, Kohno K, Iwawaki T. Akai R, et al. Cell Stress Chaperones. 2024 Feb;29(1):34-48. doi: 10.1016/j.cstres.2023.11.002. Epub 2023 Nov 20. Cell Stress Chaperones. 2024. PMID: 38320450 Free PMC article. - ATF6 is a transcription factor specializing in the regulation of quality control proteins in the endoplasmic reticulum.
Adachi Y, Yamamoto K, Okada T, Yoshida H, Harada A, Mori K. Adachi Y, et al. Cell Struct Funct. 2008;33(1):75-89. doi: 10.1247/csf.07044. Epub 2008 Mar 18. Cell Struct Funct. 2008. PMID: 18360008 - Sledgehammer to Scalpel: Broad Challenges to the Heart and Other Tissues Yield Specific Cellular Responses via Transcriptional Regulation of the ER-Stress Master Regulator ATF6α.
Stauffer WT, Arrieta A, Blackwood EA, Glembotski CC. Stauffer WT, et al. Int J Mol Sci. 2020 Feb 8;21(3):1134. doi: 10.3390/ijms21031134. Int J Mol Sci. 2020. PMID: 32046286 Free PMC article. Review. - Birth pangs: the stressful origins of lymphocytes.
Pillai S. Pillai S. J Clin Invest. 2005 Feb;115(2):224-7. doi: 10.1172/JCI24238. J Clin Invest. 2005. PMID: 15690077 Free PMC article. Review.
Cited by
- Oxidative stress, unfolded protein response, and apoptosis in developmental toxicity.
Kupsco A, Schlenk D. Kupsco A, et al. Int Rev Cell Mol Biol. 2015;317:1-66. doi: 10.1016/bs.ircmb.2015.02.002. Epub 2015 Mar 11. Int Rev Cell Mol Biol. 2015. PMID: 26008783 Free PMC article. Review. - Inhibitory effect of (pro)renin receptor decoy inhibitor PRO20 on endoplasmic reticulum stress during cardiac remodeling.
Zhang J, Cheng YJ, Luo CJ, Yu J. Zhang J, et al. Front Pharmacol. 2022 Aug 12;13:940365. doi: 10.3389/fphar.2022.940365. eCollection 2022. Front Pharmacol. 2022. PMID: 36034809 Free PMC article. - FKBP10 depletion enhances glucocerebrosidase proteostasis in Gaucher disease fibroblasts.
Ong DS, Wang YJ, Tan YL, Yates JR 3rd, Mu TW, Kelly JW. Ong DS, et al. Chem Biol. 2013 Mar 21;20(3):403-15. doi: 10.1016/j.chembiol.2012.11.014. Epub 2013 Feb 21. Chem Biol. 2013. PMID: 23434032 Free PMC article. - Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma.
Wei J, Fang D. Wei J, et al. Int J Mol Sci. 2021 Feb 11;22(4):1799. doi: 10.3390/ijms22041799. Int J Mol Sci. 2021. PMID: 33670323 Free PMC article. Review. - The endoplasmic reticulum: a sensor of cellular stress that modulates immune responses.
Martinon F. Martinon F. Microbes Infect. 2012 Nov;14(14):1293-300. doi: 10.1016/j.micinf.2012.07.005. Epub 2012 Jul 16. Microbes Infect. 2012. PMID: 22800981 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases