Premium
Transcriptional synergy between Tat and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain
Author(s) -
Dorr Alexander,
Kiermer Veronique,
Pedal Angelika,
Rackwitz HansRichard,
Henklein Peter,
Schubert Ulrich,
Zhou MingMing,
Verdin Eric,
Ott Melanie
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.11.2715
Subject(s) - pcaf , bromodomain , biology , acetylation , p300 cbp transcription factors , cancer research , microbiology and biotechnology , genetics , histone acetyltransferases , gene
The human immunodeficiency virus (HIV) Tat protein plays an essential role in promoting efficient transcriptional elongation of viral transcripts. We report that the transcriptional co‐activator PCAF and Tat interact and synergize to activate the HIV promoter. The binding of Tat and PCAF in vitro and in vivo is dependent on the acetylated state of Lys50 of Tat and on the PCAF bromodomain. Structural analysis of the acetylated Tat peptide bound to the PCAF bromodomain defined amino acids Y47 and R53 in Tat and V763, Y802, and Y809 in PCAF as critical interaction points between the two proteins. Mutation of each of these residues in either Tat or PCAF inhibited in a cumulative manner the Tat–PCAF interaction in vitro and in vivo , and abrogated the synergistic activation of the HIV promoter by both proteins. These observations demonstrate that acetylation of Tat establishes a novel protein–protein interaction domain at the surface of Tat that is necessary for the transcriptional activation of the HIV promoter.