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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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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. |
format | Online Article Text |
id | pubmed-4792581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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