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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
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.
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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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