UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation.
EMBO Rep
; 12(7): 727-34, 2011 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-21597469
ABSTRACT
Ultraviolet irradiation resistance-associated gene (UVRAG) is a well-known regulator of autophagy by promoting autophagosome formation and maturation. However, little is known about the non-autophagic functions of UVRAG. Here, we present evidence that UVRAG functions as an unusual BCL2-associated X protein (Bax) suppressor to regulate apoptosis. Chemotherapy and radiation induces UVRAG expression and subsequently upregulates autophagy and apoptosis in tumour cells. Depletion of UVRAG expression by RNA interference renders tumour cells more sensitive to chemotherapy- and radiation-induced apoptosis in vitro and in vivo. Moreover, UVRAG interacts with Bax, which inhibits apoptotic stimuli-induced mitochondrial translocation of Bax, reduction of mitochondrial membrane potential, cytochrome c release and activation of caspase-9 and -3. Our findings show that UVRAG has an essential role in the intrinsic mitochondrial pathway of apoptosis by regulating the localization of Bax. This pathway represents a target for clinical intervention against tumours.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
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Regulação Neoplásica da Expressão Gênica
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Apoptose
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Proteínas Supressoras de Tumor
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Proteína X Associada a bcl-2
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2011
Tipo de documento:
Article