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HDAC3 is negatively regulated by the nuclear protein DBC1.
Chini, Claudia C S; Escande, Carlos; Nin, Veronica; Chini, Eduardo N.
Afiliação
  • Chini CC; Laboratory of Signal Transduction, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
J Biol Chem ; 285(52): 40830-7, 2010 Dec 24.
Article em En | MEDLINE | ID: mdl-21030595
ABSTRACT
HDAC3 is a member of the class I histone deacetylase family that regulates gene expression by deacetylation of histones and non-histone proteins. HDAC3 activity has been shown to be modulated by interaction with the co-repressors NCoR and SMRT. Here, we present evidence that the nuclear protein DBC1 is an endogenous inhibitor of HDAC3. DBC1 has been previously identified as a regulator of some nuclear receptors, the methyltransferase SUV39H1, and the NAD-dependent deacetylase SIRT1. Furthermore, DBC1 has been shown to influence transcription regulation and apoptosis, and it may also act as a tumor suppressor. We found that DBC1 interacts and specifically inhibits the deacetylase HDAC3. This interaction depends on the N terminus of DBC1 and the C terminus of HDAC3. Expression of DBC1 not only inhibited HDAC3 activity but also altered its subcellular distribution. In addition, knockdown of endogenous DBC1 in cells and knock-out in mouse tissues increased HDAC3 deacetylase activity. Together, these results identify DBC1 as a new regulator of HDAC3 and demonstrate that DBC1 is a negative regulator of two key distinct deacetylases, SIRT1 and HDAC3. These findings may lead to a better understanding of the biological roles of DBC1 and HDAC3 in metabolic diseases and cancer.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Adaptadoras de Transdução de Sinal / Histona Desacetilases Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Adaptadoras de Transdução de Sinal / Histona Desacetilases Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2010 Tipo de documento: Article