Regulation of Tat acetylation and transactivation activity by the microtubule-associated deacetylase HDAC6

J Biol Chem. 2011 Mar 18;286(11):9280-6. doi: 10.1074/jbc.M110.208884. Epub 2011 Jan 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cyclin T / genetics
  • Cyclin T / metabolism
  • Gene Expression Regulation, Viral / physiology*
  • HEK293 Cells
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Histone Deacetylase 6
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Knockout
  • Microtubules / genetics
  • Microtubules / metabolism
  • Promoter Regions, Genetic / physiology
  • Transcription, Genetic / physiology*
  • Transcriptional Activation / physiology*
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • CCNT1 protein, human
  • Ccnt1 protein, mouse
  • Cyclin T
  • tat Gene Products, Human Immunodeficiency Virus
  • HDAC6 protein, human
  • Hdac6 protein, mouse
  • Histone Deacetylase 6
  • Histone Deacetylases