CREB represses p53-dependent transactivation of MDM2 through the complex formation with p53 and contributes to p53-mediated apoptosis in response to glucose deprivation.
Biochem Biophys Res Commun
; 406(1): 79-84, 2011 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-21295542
ABSTRACT
Recently, we have described that CREB (cAMP-responsive element-binding protein) has the ability to transactivate tumor suppressor p53 gene in response to glucose deprivation. In this study, we have found that CREB forms a complex with p53 and represses p53-mediated transactivation of MDM2 but not of p21(WAF1). Immunoprecipitation analysis revealed that CREB interacts with p53 in response to glucose deprivation. Forced expression of CREB significantly attenuated the up-regulation of the endogenous MDM2 in response to p53. By contrast, the mutant form of CREB lacking DNA-binding domain (CREBΔ) had an undetectable effect on the expression level of the endogenous MDM2. During the glucose deprivation-mediated apoptosis, there existed an inverse relationship between the expression levels of MDM2 and p53/CREB. Additionally, p53/CREB complex was dissociated from MDM2 promoter in response to glucose deprivation. Collectively, our present results suggest that CREB preferentially down-regulates MDM2 and thereby contributing to p53-mediated apoptosis in response to glucose deprivation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
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Proteína Supressora de Tumor p53
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Apoptose
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Proteínas Proto-Oncogênicas c-mdm2
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Glucose
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article