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PPARα induces cell apoptosis by destructing Bcl2

PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family, which plays a critical role in inhibiting cell proliferation and tumorigenesis, while the molecular mechanism is still unclear. Here we report that PPARα serves as an E3 ubiquitin ligase to govern Bcl2 protein stability...

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Autores principales: Gao, Jiaming, Liu, Qian, Xu, Ying, Gong, Xin, Zhang, Runyun, Zhou, Chenglin, Su, Zhaoliang, Jin, Jianhua, Shi, Haifeng, Shi, Juanjuan, Hou, Yongzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792581/
https://www.ncbi.nlm.nih.gov/pubmed/26556865
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author Gao, Jiaming
Liu, Qian
Xu, Ying
Gong, Xin
Zhang, Runyun
Zhou, Chenglin
Su, Zhaoliang
Jin, Jianhua
Shi, Haifeng
Shi, Juanjuan
Hou, Yongzhong
author_facet Gao, Jiaming
Liu, Qian
Xu, Ying
Gong, Xin
Zhang, Runyun
Zhou, Chenglin
Su, Zhaoliang
Jin, Jianhua
Shi, Haifeng
Shi, Juanjuan
Hou, Yongzhong
author_sort Gao, Jiaming
collection PubMed
description PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family, which plays a critical role in inhibiting cell proliferation and tumorigenesis, while the molecular mechanism is still unclear. Here we report that PPARα serves as an E3 ubiquitin ligase to govern Bcl2 protein stability. PPARα physically bound to Bcl2 protein. In this process, PPARα/C102 was critical for PPARα binding to BH3 domain of Bcl2, subsequently, PPARα transferred K48-linked polyubiquitin to lysine-22 site of Bcl2 resulting in its ubiquitination and proteasome-dependent degradation. Importantly, overexpression of PPARα enhanced cancer cell chemotherapy sensitivity. In contrast, silenced PPARα decreased this event. These findings revealed a novel mechanism of PPARα governed endogenous Bcl2 protein stability leading to reduced cancer cell chemoresistance, which provides a potential drug target for cancer treatment.
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spelling pubmed-47925812016-03-29 PPARα induces cell apoptosis by destructing Bcl2 Gao, Jiaming Liu, Qian Xu, Ying Gong, Xin Zhang, Runyun Zhou, Chenglin Su, Zhaoliang Jin, Jianhua Shi, Haifeng Shi, Juanjuan Hou, Yongzhong Oncotarget Research Paper PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family, which plays a critical role in inhibiting cell proliferation and tumorigenesis, while the molecular mechanism is still unclear. Here we report that PPARα serves as an E3 ubiquitin ligase to govern Bcl2 protein stability. PPARα physically bound to Bcl2 protein. In this process, PPARα/C102 was critical for PPARα binding to BH3 domain of Bcl2, subsequently, PPARα transferred K48-linked polyubiquitin to lysine-22 site of Bcl2 resulting in its ubiquitination and proteasome-dependent degradation. Importantly, overexpression of PPARα enhanced cancer cell chemotherapy sensitivity. In contrast, silenced PPARα decreased this event. These findings revealed a novel mechanism of PPARα governed endogenous Bcl2 protein stability leading to reduced cancer cell chemoresistance, which provides a potential drug target for cancer treatment. Impact Journals LLC 2015-11-09 /pmc/articles/PMC4792581/ /pubmed/26556865 Text en Copyright: © 2015 Gao et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
spellingShingle Research Paper
Gao, Jiaming
Liu, Qian
Xu, Ying
Gong, Xin
Zhang, Runyun
Zhou, Chenglin
Su, Zhaoliang
Jin, Jianhua
Shi, Haifeng
Shi, Juanjuan
Hou, Yongzhong
PPARα induces cell apoptosis by destructing Bcl2
title PPARα induces cell apoptosis by destructing Bcl2
title_full PPARα induces cell apoptosis by destructing Bcl2
title_fullStr PPARα induces cell apoptosis by destructing Bcl2
title_full_unstemmed PPARα induces cell apoptosis by destructing Bcl2
title_short PPARα induces cell apoptosis by destructing Bcl2
title_sort pparα induces cell apoptosis by destructing bcl2
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792581/
https://www.ncbi.nlm.nih.gov/pubmed/26556865
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