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The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters
Cytokine or growth factor activated STAT3 undergoes multiple post-translational modifications, dimerization and translocation into nuclei, where it binds to serum-inducible element (SIE, ‘TTC(N3)GAA’)-bearing promoters to activate transcription. The STAT3 DNA binding domain (DBD, 320–494) mutation i...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605325/ https://www.ncbi.nlm.nih.gov/pubmed/26384563 http://dx.doi.org/10.1093/nar/gkv911 |
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author | Xu, Li Ji, Jin-Jun Le, Wangping Xu, Yan S. Dou, Dandan Pan, Jieli Jiao, Yifeng Zhong, Tianfei Wu, Dehong Wang, Yumei Wen, Chengping Xie, Guan-Qun Yao, Feng Zhao, Heng Fan, Yong-Sheng Chin, Y. Eugene |
author_facet | Xu, Li Ji, Jin-Jun Le, Wangping Xu, Yan S. Dou, Dandan Pan, Jieli Jiao, Yifeng Zhong, Tianfei Wu, Dehong Wang, Yumei Wen, Chengping Xie, Guan-Qun Yao, Feng Zhao, Heng Fan, Yong-Sheng Chin, Y. Eugene |
author_sort | Xu, Li |
collection | PubMed |
description | Cytokine or growth factor activated STAT3 undergoes multiple post-translational modifications, dimerization and translocation into nuclei, where it binds to serum-inducible element (SIE, ‘TTC(N3)GAA’)-bearing promoters to activate transcription. The STAT3 DNA binding domain (DBD, 320–494) mutation in hyper immunoglobulin E syndrome (HIES), called the HIES mutation (R382Q, R382W or V463Δ), which elevates IgE synthesis, inhibits SIE binding activity and sensitizes genes such as TNF-α for expression. However, the mechanism by which the HIES mutation sensitizes STAT3 in gene induction remains elusive. Here, we report that STAT3 binds directly to the AGG-element with the consensus sequence ‘AGG(N3)AGG’. Surprisingly, the helical N-terminal region (1–355), rather than the canonical STAT3 DBD, is responsible for AGG-element binding. The HIES mutation markedly enhances STAT3 AGG-element binding and AGG-promoter activation activity. Thus, STAT3 is a dual specificity transcription factor that promotes gene expression not only via SIE- but also AGG-promoter activity. |
format | Online Article Text |
id | pubmed-4605325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-46053252015-10-19 The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters Xu, Li Ji, Jin-Jun Le, Wangping Xu, Yan S. Dou, Dandan Pan, Jieli Jiao, Yifeng Zhong, Tianfei Wu, Dehong Wang, Yumei Wen, Chengping Xie, Guan-Qun Yao, Feng Zhao, Heng Fan, Yong-Sheng Chin, Y. Eugene Nucleic Acids Res Molecular Biology Cytokine or growth factor activated STAT3 undergoes multiple post-translational modifications, dimerization and translocation into nuclei, where it binds to serum-inducible element (SIE, ‘TTC(N3)GAA’)-bearing promoters to activate transcription. The STAT3 DNA binding domain (DBD, 320–494) mutation in hyper immunoglobulin E syndrome (HIES), called the HIES mutation (R382Q, R382W or V463Δ), which elevates IgE synthesis, inhibits SIE binding activity and sensitizes genes such as TNF-α for expression. However, the mechanism by which the HIES mutation sensitizes STAT3 in gene induction remains elusive. Here, we report that STAT3 binds directly to the AGG-element with the consensus sequence ‘AGG(N3)AGG’. Surprisingly, the helical N-terminal region (1–355), rather than the canonical STAT3 DBD, is responsible for AGG-element binding. The HIES mutation markedly enhances STAT3 AGG-element binding and AGG-promoter activation activity. Thus, STAT3 is a dual specificity transcription factor that promotes gene expression not only via SIE- but also AGG-promoter activity. Oxford University Press 2015-10-15 2015-10-10 /pmc/articles/PMC4605325/ /pubmed/26384563 http://dx.doi.org/10.1093/nar/gkv911 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular Biology Xu, Li Ji, Jin-Jun Le, Wangping Xu, Yan S. Dou, Dandan Pan, Jieli Jiao, Yifeng Zhong, Tianfei Wu, Dehong Wang, Yumei Wen, Chengping Xie, Guan-Qun Yao, Feng Zhao, Heng Fan, Yong-Sheng Chin, Y. Eugene The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters |
title | The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters |
title_full | The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters |
title_fullStr | The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters |
title_full_unstemmed | The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters |
title_short | The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters |
title_sort | stat3 hies mutation is a gain-of-function mutation that activates genes via agg-element carrying promoters |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605325/ https://www.ncbi.nlm.nih.gov/pubmed/26384563 http://dx.doi.org/10.1093/nar/gkv911 |
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