Activation of TR4 orphan nuclear receptor gene promoter by cAMP/PKA and C/EBP signaling.
Endocrine
; 36(2): 211-7, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19618297
ABSTRACT
In earlier studies, we had suggested that the fasting signal induces TR4 orphan nuclear receptor expression in vivo. The detailed mechanism(s), however, remain unclear. In this study, we found that cAMP/PKA, the mediator of fasting and glucagon signals, could induce TR4 gene expression that in turn modulates gluconeogenesis. Mechanistic dissection by in vitro studies in hepatocytes demonstrated that cAMP/PKA might trigger C/EBP alpha and beta binding to the selective cAMP response element, which is located at the TR4 promoter, thus inducing TR4 transcription. We also demonstrated that the binding activity of C/EBPs to the TR4 promoter is increased in response to cAMP treatment. Together, our data identified a new signaling pathway from the fasting signal --> cAMP/PKA --> C/EBP alpha and beta --> TR4 --> gluconeogenesis in hepatocytes; and suggested that TR4 could be an important regulator to control glucose homeostasis. The identification of activator(s)/inhibitor(s) or ligand(s) of TR4 may provide us an alternative way to control gluconeogenesis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores dos Hormônios Tireóideos
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Receptores de Esteroides
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Ativação Transcricional
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Regiões Promotoras Genéticas
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Proteínas Quinases Dependentes de AMP Cíclico
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AMP Cíclico
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Proteínas Estimuladoras de Ligação a CCAAT
Limite:
Humans
Idioma:
En
Revista:
Endocrine
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos