Regulation of Tat acetylation and transactivation activity by the microtubule-associated deacetylase HDAC6.
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.
Mesh Terms:
Acetylation, Animals, Cyclin T, Gene Expression Regulation, Viral, HEK293 Cells, HIV-1, Histone Deacetylases, Humans, Jurkat Cells, Mice, Mice, Knockout, Microtubules, Promoter Regions, Genetic, Transcription, Genetic, Transcriptional Activation, tat Gene Products, Human Immunodeficiency Virus
Acetylation, Animals, Cyclin T, Gene Expression Regulation, Viral, HEK293 Cells, HIV-1, Histone Deacetylases, Humans, Jurkat Cells, Mice, Mice, Knockout, Microtubules, Promoter Regions, Genetic, Transcription, Genetic, Transcriptional Activation, tat Gene Products, Human Immunodeficiency Virus
J. Biol. Chem.
Date: Mar. 18, 2011
PubMed ID: 21220424
View in: Pubmed Google Scholar
Download Curated Data For This Publication
118561
Switch View:
- Interactions 8