Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication.
The human immunodeficiency virus type-1 trans-activator Tat is a transcription factor that activates the HIV-1 promoter through binding to the trans-activation-responsive region (TAR) localized at the 5'-end of all viral transcripts. We and others have recently shown that Tat is directly acetylated at lysine 28, within the activation domain, and lysine 50, in the TAR RNA binding domain, by Tat-associated histone acetyltransferases p300, p300/CBP-associating factor, and hGCN5. Here, we show that mutation of acetyl-acceptor lysines to arginine or glutamine affects virus replication. Interestingly, mutation of lysine 28 and lysine 50 differentially affected Tat trans-activation of integrated versus nonintegrated long terminal repeat. Our results highlight the importance of lysine 28 and lysine 50 of Tat in virus replication and Tat-mediated trans-activation.
Brès
Vanessa
V
Institut de Génétique Humaine, CNRS UPR 1142, 141 rue de la Cardonille, 34396 Montpellier cedex 5, France.
Kiernan
Rosemary
R
Emiliani
Stéphane
S
Benkirane
Monsef
M
D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D015153:Blotting, Western; D015696:Gene Products, tat / Q000378:metabolism*; D005973:Glutamine / Q000737:chemistry; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D020079:Terminal Repeat Sequences; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D005973:Glutamine; D001120:Arginine; D008239:Lysine