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TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene
Tumor suppressor p53 transcriptionally regulates hundreds of genes involved in various cellular functions. However, the detailed mechanisms underlying the selection of p53 targets in response to different stresses are still elusive. Here, we identify TFIIS.h, a transcription elongation factor, as a...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804275/ https://www.ncbi.nlm.nih.gov/pubmed/27005522 http://dx.doi.org/10.1038/srep23542 |
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author | Liao, Jun-Ming Cao, Bo Deng, Jun Zhou, Xiang Strong, Michael Zeng, Shelya Xiong, Jianping Flemington, Erik Lu, Hua |
author_facet | Liao, Jun-Ming Cao, Bo Deng, Jun Zhou, Xiang Strong, Michael Zeng, Shelya Xiong, Jianping Flemington, Erik Lu, Hua |
author_sort | Liao, Jun-Ming |
collection | PubMed |
description | Tumor suppressor p53 transcriptionally regulates hundreds of genes involved in various cellular functions. However, the detailed mechanisms underlying the selection of p53 targets in response to different stresses are still elusive. Here, we identify TFIIS.h, a transcription elongation factor, as a new transcriptional target of p53, and also show that it can enhance the efficiency of transcription elongation of apoptosis-associated bax gene, but not cell cycle-associated p21 (CDKN1A) gene. TFIIS.h is revealed as a p53 target through microarray analysis of RNAs extracted from cells treated with or without inauhzin (INZ), a p53 activator, and further confirmed by RT-q-PCR, western blot, luciferase reporter, and ChIP assays. Interestingly, knocking down TFIIS.h impairs, but overexpressing TFIIS.h promotes, induction of bax, but not other p53 targets including p21, by p53 activation. In addition, overexpression of TFIIS.h induces cell death in a bax- dependent fashion. These findings reveal a mechanism by which p53 utilizes TFIIS.h to selectively promote the transcriptional elongation of the bax gene, upsurging cell death in response to severe DNA damage. |
format | Online Article Text |
id | pubmed-4804275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48042752016-03-23 TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene Liao, Jun-Ming Cao, Bo Deng, Jun Zhou, Xiang Strong, Michael Zeng, Shelya Xiong, Jianping Flemington, Erik Lu, Hua Sci Rep Article Tumor suppressor p53 transcriptionally regulates hundreds of genes involved in various cellular functions. However, the detailed mechanisms underlying the selection of p53 targets in response to different stresses are still elusive. Here, we identify TFIIS.h, a transcription elongation factor, as a new transcriptional target of p53, and also show that it can enhance the efficiency of transcription elongation of apoptosis-associated bax gene, but not cell cycle-associated p21 (CDKN1A) gene. TFIIS.h is revealed as a p53 target through microarray analysis of RNAs extracted from cells treated with or without inauhzin (INZ), a p53 activator, and further confirmed by RT-q-PCR, western blot, luciferase reporter, and ChIP assays. Interestingly, knocking down TFIIS.h impairs, but overexpressing TFIIS.h promotes, induction of bax, but not other p53 targets including p21, by p53 activation. In addition, overexpression of TFIIS.h induces cell death in a bax- dependent fashion. These findings reveal a mechanism by which p53 utilizes TFIIS.h to selectively promote the transcriptional elongation of the bax gene, upsurging cell death in response to severe DNA damage. Nature Publishing Group 2016-03-23 /pmc/articles/PMC4804275/ /pubmed/27005522 http://dx.doi.org/10.1038/srep23542 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Liao, Jun-Ming Cao, Bo Deng, Jun Zhou, Xiang Strong, Michael Zeng, Shelya Xiong, Jianping Flemington, Erik Lu, Hua TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
title | TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
title_full | TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
title_fullStr | TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
title_full_unstemmed | TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
title_short | TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
title_sort | tfiis.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804275/ https://www.ncbi.nlm.nih.gov/pubmed/27005522 http://dx.doi.org/10.1038/srep23542 |
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