Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity.
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 he 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.
Ott
M
M
Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, 69120, Germany.
Schnölzer
M
M
Garnica
J
J
Fischle
W
W
Emiliani
S
S
Rackwitz
H R
HR
Verdin
E
E
D000107:Acetylation; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D009687:Nuclear Proteins; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus