PPARα induces cell apoptosis by destructing Bcl2
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Jiaming Gao1,2,*, Qian Liu1,*, Ying Xu2, Xin Gong2, Runyun Zhang2, Chenglin Zhou3, Zhaoliang Su4, Jianhua Jin1, Haifeng Shi2, Juanjuan Shi2, Yongzhong Hou1,2
1Department of Oncology, The Affiliated Wujin People's Hospital, Jiangsu University, Changzhou, Jiangsu Province, China
2Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China
3Jiangsu Taizhou People's Hospital, Jiangsu Province, China
4Department of Immunology & Laboratory Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
*These authors have contributed equally to this work
Juanjuan Shi, e-mail: firstname.lastname@example.org
Yongzhong Hou, e-mail: email@example.com
Keywords: ubiquitination, degradation, apoptosis, PPARα, Bcl2
Received: June 24, 2015 Accepted: October 01, 2015 Published: November 09, 2015
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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