PPARα induces cell apoptosis by destructing Bcl2.
Oncotarget
; 6(42): 44635-42, 2015 Dec 29.
Article
em En
| MEDLINE
| ID: mdl-26556865
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Proteínas Proto-Oncogênicas c-bcl-2
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Ubiquitina-Proteína Ligases
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PPAR alfa
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China