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Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK

Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria through interaction with Bcl-2, an event that converts Bcl-2 from a survival to killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains largely unknown. In this study, we examined the regulation of the Nur...

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Autores principales: Liu, Jie, Wang, Guang-Hui, Duan, Ying-Hui, Dai, Yi, Bao, Yuzhou, Hu, Mengjie, Zhou, Yu-Qi, Li, Mingyu, Jiang, Fuquan, Zhou, Hu, Yao, Xin-Sheng, Zhang, Xiao-Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642512/
https://www.ncbi.nlm.nih.gov/pubmed/29050237
http://dx.doi.org/10.18632/oncotarget.19227
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author Liu, Jie
Wang, Guang-Hui
Duan, Ying-Hui
Dai, Yi
Bao, Yuzhou
Hu, Mengjie
Zhou, Yu-Qi
Li, Mingyu
Jiang, Fuquan
Zhou, Hu
Yao, Xin-Sheng
Zhang, Xiao-Kun
author_facet Liu, Jie
Wang, Guang-Hui
Duan, Ying-Hui
Dai, Yi
Bao, Yuzhou
Hu, Mengjie
Zhou, Yu-Qi
Li, Mingyu
Jiang, Fuquan
Zhou, Hu
Yao, Xin-Sheng
Zhang, Xiao-Kun
author_sort Liu, Jie
collection PubMed
description Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria through interaction with Bcl-2, an event that converts Bcl-2 from a survival to killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains largely unknown. In this study, we examined the regulation of the Nur77-Bcl-2 pathway by CCE9, a xanthone compound. Our results demonstrated that the apoptotic effect of CCE9 depended on its induction of Nur77 expression, cytoplasmic localization, and mitochondrial targeting. The activation of the Nur77-Bcl-2 pathway by CCE9 was associated with its activation of p38α MAPK. Inhibition of p38α MAPK activation by knocking down or knocking out p38α MAPK impaired the effect of CCE9 on inducing apoptosis and the expression and cytoplasmic localization of Nur77. In addition, CCE9 activation of p38α MAPK resulted in Bcl-2 phosphorylation and Bcl-2 interaction with Nur77, whereas inhibition of p38α MAPK activation or expression suppressed the interaction. Moreover, mutating Ser87 and Thr56 in the loop of Bcl-2, which are known to be phosphorylated by p38α MAPK, impaired the ability Bcl-2 to interact with Nur77. Together, our results reveal a profound role of p38α MAPK in regulating the Nur77-Bcl-2 apoptotic pathway through its modulation of Nur77 expression, Bcl-2 phosphorylation, and their interaction.
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spelling pubmed-56425122017-10-18 Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK Liu, Jie Wang, Guang-Hui Duan, Ying-Hui Dai, Yi Bao, Yuzhou Hu, Mengjie Zhou, Yu-Qi Li, Mingyu Jiang, Fuquan Zhou, Hu Yao, Xin-Sheng Zhang, Xiao-Kun Oncotarget Research Paper Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria through interaction with Bcl-2, an event that converts Bcl-2 from a survival to killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains largely unknown. In this study, we examined the regulation of the Nur77-Bcl-2 pathway by CCE9, a xanthone compound. Our results demonstrated that the apoptotic effect of CCE9 depended on its induction of Nur77 expression, cytoplasmic localization, and mitochondrial targeting. The activation of the Nur77-Bcl-2 pathway by CCE9 was associated with its activation of p38α MAPK. Inhibition of p38α MAPK activation by knocking down or knocking out p38α MAPK impaired the effect of CCE9 on inducing apoptosis and the expression and cytoplasmic localization of Nur77. In addition, CCE9 activation of p38α MAPK resulted in Bcl-2 phosphorylation and Bcl-2 interaction with Nur77, whereas inhibition of p38α MAPK activation or expression suppressed the interaction. Moreover, mutating Ser87 and Thr56 in the loop of Bcl-2, which are known to be phosphorylated by p38α MAPK, impaired the ability Bcl-2 to interact with Nur77. Together, our results reveal a profound role of p38α MAPK in regulating the Nur77-Bcl-2 apoptotic pathway through its modulation of Nur77 expression, Bcl-2 phosphorylation, and their interaction. Impact Journals LLC 2017-07-13 /pmc/articles/PMC5642512/ /pubmed/29050237 http://dx.doi.org/10.18632/oncotarget.19227 Text en Copyright: © 2017 Liu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Jie
Wang, Guang-Hui
Duan, Ying-Hui
Dai, Yi
Bao, Yuzhou
Hu, Mengjie
Zhou, Yu-Qi
Li, Mingyu
Jiang, Fuquan
Zhou, Hu
Yao, Xin-Sheng
Zhang, Xiao-Kun
Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK
title Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK
title_full Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK
title_fullStr Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK
title_full_unstemmed Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK
title_short Modulation of the Nur77-Bcl-2 apoptotic pathway by p38α MAPK
title_sort modulation of the nur77-bcl-2 apoptotic pathway by p38α mapk
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642512/
https://www.ncbi.nlm.nih.gov/pubmed/29050237
http://dx.doi.org/10.18632/oncotarget.19227
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