title: PPARα induces cell apoptosis by destructing Bcl2.
abstract: 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.
authors.affiliation: Department of Oncology, The Affiliated Wujin People's Hospital, Jiangsu University, Changzhou, Jiangsu Province, China.|Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Oncology, The Affiliated Wujin People's Hospital, Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gong
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Runyun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Jiangsu Taizhou People's Hospital, Jiangsu Province, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Immunology & Laboratory Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Oncology, The Affiliated Wujin People's Hospital, Jiangsu University, Changzhou, Jiangsu Province, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Jin
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shi
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Oncology, The Affiliated Wujin People's Hospital, Jiangsu University, Changzhou, Jiangsu Province, China.|Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D059748:Proteolysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; D047493:PPAR alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Bcl2; PPARα; apoptosis; degradation; ubiquitination