Acetylation of the HIV-1 tat protein by p300 is important for its transcriptional activity

Melanie Ott, Martina Schnölzer, Jerry Garnica, Wolfgang Fischle, Stephane Emiliani, Hans Richard Rackwitz, Eric Verdin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

253 Scopus citations

Abstract

The human immunodeficiency virus 1 (HIV-1) Tat protein activates transcriptional elongation by recruiting the positive transcription elongation factor (pTEFb) complex to the TAR RNA element, which is located at the 5' extremity of all viral transcripts [1-3]. Tat also associates in vitro and in vivo with the transcriptional coactivator p300/CBP [4-6]. This association has been proposed to recruit the histone acetyltransferase (HAT) activity of p300 to the integrated HIV-1 promoter. We have observed that the purified p300 HAT domain acetylates recombinant Tat proteins in vitro and that Tat is acetylated in vivo. The major targets of acetylation by p300 are lysine residues (Lys50 and Lys51) in the arginine-rich motif (ARM) used by Tat to bind RNA and for nuclear import. Mutation of these residues in full-length recombinant Tat blocked its acetylation in vitro. Furthermore, mutation of these lysine residues to arginine markedly decreased the synergistic activation of the HIV promoter by Tat and p300 or by Tat and cyclin T1. These results demonstrate that acetylation of Tat by p300/CBP is important for its transcriptional activation of the HIV promoter.

Original languageEnglish (US)
Pages (from-to)1489-1493
Number of pages5
JournalCurrent Biology
Volume9
Issue number24
DOIs
StatePublished - Dec 16 1999

Bibliographical note

Funding Information:
We thank Carol Ann Amella and Carine Van Lint for the LTR–luciferase constructs, Kathy Jones for the cyclin T1 expression vector, Naren Chirmule for Tat peptides, Birgit Hub for performing the indirect immunofluorescence analysis of wild-type and mutant Tat proteins, and Harald zur Hausen and Kathy Jones for helpful discussions. We thank John C.W. Carroll and Neile Shea for graphics, Heather Gravois for manuscript preparation, and Stephen Ordway and Gary Howard for editorial assistance. This work was supported in part by a Public Health Service grant from the NIH, by the Deutsches Krebsforschungszentrum (DKFZ) and by the Gladstone Institute of Virology and Immunology.

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

Fingerprint

Dive into the research topics of 'Acetylation of the HIV-1 tat protein by p300 is important for its transcriptional activity'. Together they form a unique fingerprint.

Cite this