Regulation of Tat acetylation and transactivation activity by the microtubule-associated deacetylase HDAC6.
J Biol Chem
; 286(11): 9280-6, 2011 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-21220424
ABSTRACT
Reversible acetylation of Tat is critical for its transactivation activity toward HIV-1 transcription. However, the enzymes involved in the acetylation/deacetylation cycles have not been fully characterized. In this study, by yeast two-hybrid assay, we have discovered the histone deacetylase HDAC6 to be a binding partner of Tat. Our data show that HDAC6 interacts with Tat in the cytoplasm in a microtubule-dependent manner. In addition, HDAC6 deacetylates Tat at Lys-28 and thereby suppresses Tat-mediated transactivation of the HIV-1 promoter. Inactivation of HDAC6 promotes the interaction of Tat with cyclin T1 and leads to an increase in Tat transactivation activity. These findings establish HDAC6 as a Tat deacetylase and support a model in which Lys-28 deacetylation decreases Tat transactivation activity through affecting the ability of Tat to form a ribonucleoprotein complex with cyclin T1 and the transactivation-responsive RNA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Regulação Viral da Expressão Gênica
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Ativação Transcricional
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HIV-1
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Produtos do Gene tat do Vírus da Imunodeficiência Humana
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Histona Desacetilases
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China