The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat.
Factor acetyltransferase activity associated with several histone acetyltransferases plays a key role in the control of transcription. Here we report that hGCN5, a well known histone acetyltransferase, specifically interacts with and acetylates the human immunodeficiency virus type 1 (HIV-1) transactivator protein, Tat. The interaction between Tat and hGCN5 is direct and involves the acetyltransferase and the bromodomain regions of hGCN5, as well as a limited region of Tat encompassing the cysteine-rich domain of the protein. Tat lysines 50 and 51, target of acetylation by p300/CBP, were also found to be acetylated by hGCN5. The acetylation of these two lysines by p300/CBP has been recently shown to stimulate Tat transcriptional activity and accordingly, we have found that hGCN5 can considerably enhance Tat-dependent transcription of the HIV-1 long terminal repeat. These data highlight the importance of the acetylation of lysines 50 and 51 in the function of Tat, since different histone acetyltransferases involved in distinct signaling pathways, GCN5 and p300/CBP, converge to acetylate Tat on the same site.
Col
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E
Laboratoire de Biologie du Stress Oxydant, Faculté de Pharmacie, Domaine de la Merci, 38700 La Tronche Cedex, France.
Caron
C
C
Seigneurin-Berny
D
D
Gracia
J
J
Favier
A
A
Khochbin
S
S
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism*; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D020079:Terminal Repeat Sequences; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D015696:Gene Products, tat; D005982:Glutathione Transferase; D051548:Histone Acetyltransferases; D006657:Histones; D008156:Luciferases; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C501179:KAT2A protein, human