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Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation

BACKGROUND: Induction of apoptosis by endoplasmic reticulum (ER) stress is implicated as the major factor in the development of multiple diseases. ER stress also appears to be a potentially useful major response to many chemotherapeutic drugs and environmental chemical compounds. A previous study ha...

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Autores principales: Lin, Wan-Chi, Chuang, Yu-Chi, Chang, Yung-Sheng, Lai, Ming-Derg, Teng, Yen-Ni, Su, Ih-Jen, Wang, Clay C. C., Lee, Kuan-Han, Hung, Jui-Hsiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408479/
https://www.ncbi.nlm.nih.gov/pubmed/22859938
http://dx.doi.org/10.1371/journal.pone.0039120
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author Lin, Wan-Chi
Chuang, Yu-Chi
Chang, Yung-Sheng
Lai, Ming-Derg
Teng, Yen-Ni
Su, Ih-Jen
Wang, Clay C. C.
Lee, Kuan-Han
Hung, Jui-Hsiang
author_facet Lin, Wan-Chi
Chuang, Yu-Chi
Chang, Yung-Sheng
Lai, Ming-Derg
Teng, Yen-Ni
Su, Ih-Jen
Wang, Clay C. C.
Lee, Kuan-Han
Hung, Jui-Hsiang
author_sort Lin, Wan-Chi
collection PubMed
description BACKGROUND: Induction of apoptosis by endoplasmic reticulum (ER) stress is implicated as the major factor in the development of multiple diseases. ER stress also appears to be a potentially useful major response to many chemotherapeutic drugs and environmental chemical compounds. A previous study has indicated that one major apoptotic regulator, p53, is significantly increased in response to ER stress, and participates in ER stress-induced apoptosis. However, the regulators of p53 expression during ER stress are still not fully understood. PRINCIPAL FINDINGS: In this report, we demonstrate that induction of p53 expression is mediated through NF-κB signaling pathways during ER stress in MCF-7 cells. Tunicamycin or brefeldin A, two ER stress inducers, increased p53 expression in MCF-7 and Hela cells. We found p53 nuclear localization, activity, and phosphorylation at serine 15 on p53 increased during ER stress. Nuclear translocation of NF-κB and activity of NF-κB were also observed during ER stress. ER stress-induced p53 expression was significantly inhibited by coincubation with the NF-κB inhibitor, Bay 11-7082 and downregulation of NF-κB p65 expression. The role of p53 in mediating Brefeldin A-induced apoptosis was also investigated. Induction of p53 expression by Brefeldin A was correlated to Brefeldin A-induced apoptosis. Furthermore, downregulation of p53 expression by p53 siRNA significantly reduced Brefeldin A-induced apoptosis in MCF-7 cells. SIGNIFICANCE: Taken together, NF-κB activation and induction of p53 expression is essential for ER stress-induced cell death which is important for therapeutic effects of clinical cancer drugs. Our results may provide insight into the mechanism of cancer chemotherapy efficacy that is associated with induction of ER stress.
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spelling pubmed-34084792012-08-02 Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation Lin, Wan-Chi Chuang, Yu-Chi Chang, Yung-Sheng Lai, Ming-Derg Teng, Yen-Ni Su, Ih-Jen Wang, Clay C. C. Lee, Kuan-Han Hung, Jui-Hsiang PLoS One Research Article BACKGROUND: Induction of apoptosis by endoplasmic reticulum (ER) stress is implicated as the major factor in the development of multiple diseases. ER stress also appears to be a potentially useful major response to many chemotherapeutic drugs and environmental chemical compounds. A previous study has indicated that one major apoptotic regulator, p53, is significantly increased in response to ER stress, and participates in ER stress-induced apoptosis. However, the regulators of p53 expression during ER stress are still not fully understood. PRINCIPAL FINDINGS: In this report, we demonstrate that induction of p53 expression is mediated through NF-κB signaling pathways during ER stress in MCF-7 cells. Tunicamycin or brefeldin A, two ER stress inducers, increased p53 expression in MCF-7 and Hela cells. We found p53 nuclear localization, activity, and phosphorylation at serine 15 on p53 increased during ER stress. Nuclear translocation of NF-κB and activity of NF-κB were also observed during ER stress. ER stress-induced p53 expression was significantly inhibited by coincubation with the NF-κB inhibitor, Bay 11-7082 and downregulation of NF-κB p65 expression. The role of p53 in mediating Brefeldin A-induced apoptosis was also investigated. Induction of p53 expression by Brefeldin A was correlated to Brefeldin A-induced apoptosis. Furthermore, downregulation of p53 expression by p53 siRNA significantly reduced Brefeldin A-induced apoptosis in MCF-7 cells. SIGNIFICANCE: Taken together, NF-κB activation and induction of p53 expression is essential for ER stress-induced cell death which is important for therapeutic effects of clinical cancer drugs. Our results may provide insight into the mechanism of cancer chemotherapy efficacy that is associated with induction of ER stress. Public Library of Science 2012-07-30 /pmc/articles/PMC3408479/ /pubmed/22859938 http://dx.doi.org/10.1371/journal.pone.0039120 Text en © 2012 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lin, Wan-Chi
Chuang, Yu-Chi
Chang, Yung-Sheng
Lai, Ming-Derg
Teng, Yen-Ni
Su, Ih-Jen
Wang, Clay C. C.
Lee, Kuan-Han
Hung, Jui-Hsiang
Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation
title Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation
title_full Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation
title_fullStr Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation
title_full_unstemmed Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation
title_short Endoplasmic Reticulum Stress Stimulates p53 Expression through NF-κB Activation
title_sort endoplasmic reticulum stress stimulates p53 expression through nf-κb activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408479/
https://www.ncbi.nlm.nih.gov/pubmed/22859938
http://dx.doi.org/10.1371/journal.pone.0039120
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