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Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells
Stress response gene ATF3 plays a pleiotropic role in determining cell fate in response to mitogenic or stress stimuli. An alternate promoter of the human ATF3 gene (designated P1 in this study) has recently been reported, which is located ∼43.5 kb upstream of the previously reported P2 promoter. We...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655689/ https://www.ncbi.nlm.nih.gov/pubmed/19136462 http://dx.doi.org/10.1093/nar/gkn1082 |
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author | Miyazaki, Keisuke Inoue, Shoko Yamada, Kazuhiko Watanabe, Masashi Liu, Qin Watanabe, Toshiki Adachi, Mimi Tamamori Tanaka, Yujiro Kitajima, Shigetaka |
author_facet | Miyazaki, Keisuke Inoue, Shoko Yamada, Kazuhiko Watanabe, Masashi Liu, Qin Watanabe, Toshiki Adachi, Mimi Tamamori Tanaka, Yujiro Kitajima, Shigetaka |
author_sort | Miyazaki, Keisuke |
collection | PubMed |
description | Stress response gene ATF3 plays a pleiotropic role in determining cell fate in response to mitogenic or stress stimuli. An alternate promoter of the human ATF3 gene (designated P1 in this study) has recently been reported, which is located ∼43.5 kb upstream of the previously reported P2 promoter. We showed here that the P1 promoter is highly conserved between human and mouse and is functional in response to various stimuli, whereas the P1 promoter was dominantly induced by serum and the P2 promoter was more efficiently activated in response to TGF-β and oncogenic HRAS. The P1 promoter contains multiple transcriptional start sites, and the different 5′-UTRs markedly affected their translation in response to stress. In human prostate and Hodgkin Reed–Sternberg cancer cells with elevated expression of ATF3, the P1 promoter was constitutively activated and its chromatin structure was modified into active configuration. The differential usage of alternate promoters of the ATF3 gene at both transcriptional and translational level and the modification of chromatin structure may provide a novel mechanism for expressing ATF3 in determining cell fate during stress response and cancer. |
format | Text |
id | pubmed-2655689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26556892009-04-01 Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells Miyazaki, Keisuke Inoue, Shoko Yamada, Kazuhiko Watanabe, Masashi Liu, Qin Watanabe, Toshiki Adachi, Mimi Tamamori Tanaka, Yujiro Kitajima, Shigetaka Nucleic Acids Res Molecular Biology Stress response gene ATF3 plays a pleiotropic role in determining cell fate in response to mitogenic or stress stimuli. An alternate promoter of the human ATF3 gene (designated P1 in this study) has recently been reported, which is located ∼43.5 kb upstream of the previously reported P2 promoter. We showed here that the P1 promoter is highly conserved between human and mouse and is functional in response to various stimuli, whereas the P1 promoter was dominantly induced by serum and the P2 promoter was more efficiently activated in response to TGF-β and oncogenic HRAS. The P1 promoter contains multiple transcriptional start sites, and the different 5′-UTRs markedly affected their translation in response to stress. In human prostate and Hodgkin Reed–Sternberg cancer cells with elevated expression of ATF3, the P1 promoter was constitutively activated and its chromatin structure was modified into active configuration. The differential usage of alternate promoters of the ATF3 gene at both transcriptional and translational level and the modification of chromatin structure may provide a novel mechanism for expressing ATF3 in determining cell fate during stress response and cancer. Oxford University Press 2009-04 2009-01-09 /pmc/articles/PMC2655689/ /pubmed/19136462 http://dx.doi.org/10.1093/nar/gkn1082 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular Biology Miyazaki, Keisuke Inoue, Shoko Yamada, Kazuhiko Watanabe, Masashi Liu, Qin Watanabe, Toshiki Adachi, Mimi Tamamori Tanaka, Yujiro Kitajima, Shigetaka Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells |
title | Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells |
title_full | Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells |
title_fullStr | Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells |
title_full_unstemmed | Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells |
title_short | Differential usage of alternate promoters of the human stress response gene ATF3 in stress response and cancer cells |
title_sort | differential usage of alternate promoters of the human stress response gene atf3 in stress response and cancer cells |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655689/ https://www.ncbi.nlm.nih.gov/pubmed/19136462 http://dx.doi.org/10.1093/nar/gkn1082 |
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