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The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity
The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluoresc...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684815/ https://www.ncbi.nlm.nih.gov/pubmed/23774320 http://dx.doi.org/10.1038/srep02006 |
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author | Zhang, Yiguo Hayes, John D. |
author_facet | Zhang, Yiguo Hayes, John D. |
author_sort | Zhang, Yiguo |
collection | PubMed |
description | The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression. |
format | Online Article Text |
id | pubmed-3684815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-36848152013-06-24 The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity Zhang, Yiguo Hayes, John D. Sci Rep Article The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression. Nature Publishing Group 2013-06-18 /pmc/articles/PMC3684815/ /pubmed/23774320 http://dx.doi.org/10.1038/srep02006 Text en Copyright © 2013, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Zhang, Yiguo Hayes, John D. The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity |
title | The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity |
title_full | The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity |
title_fullStr | The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity |
title_full_unstemmed | The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity |
title_short | The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity |
title_sort | membrane-topogenic vectorial behaviour of nrf1 controls its post-translational modification and transactivation activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684815/ https://www.ncbi.nlm.nih.gov/pubmed/23774320 http://dx.doi.org/10.1038/srep02006 |
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