Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation

Mol Cell. 2003 Jul;12(1):167-76. doi: 10.1016/s1097-2765(03)00245-4.


The HIV transcriptional activator Tat is acetylated by p300 at a single lysine residue in the TAR RNA binding domain. We have generated monoclonal and polyclonal antibodies specific for the acetylated form of Tat (AcTat). Microinjection of anti-AcTat antibodies inhibited Tat-mediated transactivation in cells. Similarly, the p300 inhibitor Lys-CoA and siRNA specific for p300 suppressed Tat transcriptional activity. Full-length synthetic AcTat bound to TAR RNA with the same affinity as unacetylated Tat, but formation of a Tat-TAR-CyclinT1 ternary complex was completely inhibited in the presence of AcTat. We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Acetyltransferases / antagonists & inhibitors
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Antibodies
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin T
  • Cyclins / genetics*
  • Gene Products, tat / antagonists & inhibitors
  • Gene Products, tat / genetics*
  • Gene Products, tat / metabolism*
  • HIV Long Terminal Repeat / genetics
  • HIV-1 / genetics*
  • HeLa Cells
  • Histone Acetyltransferases
  • Humans
  • Jurkat Cells
  • Macromolecular Substances
  • Models, Molecular
  • RNA Polymerase II / biosynthesis
  • RNA Polymerase II / genetics
  • RNA, Small Interfering / pharmacology
  • Transcription Factors
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics*
  • p300-CBP Transcription Factors
  • tat Gene Products, Human Immunodeficiency Virus


  • Antibodies
  • CCNT1 protein, human
  • Cell Cycle Proteins
  • Cyclin T
  • Cyclins
  • Gene Products, tat
  • Macromolecular Substances
  • RNA, Small Interfering
  • Transcription Factors
  • tat Gene Products, Human Immunodeficiency Virus
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • RNA Polymerase II