The human immunodeficiency virus type 1 Tat protein transactivates tumor necrosis factor beta gene expression through a TAR-like structure.
We have previously shown that the Tat protein of human immunodeficiency virus type 1 (HIV-1) transactivates tumor necrosis factor alpha and beta (TNF alpha and TNF beta) gene expression in HIV-1-infected and in tat-transfected T-lymphocytic and monocytic cell lines. The product encoded by the first exon of the tat gene (amino acids 1 to 72) is sufficient for this transactivation. Here we show that (i) the NF-kappa B and Sp1 binding sites of the TNF beta promoter are required for Tat-mediated transactivation and (ii) a predicted stem-loop structure in the TNF beta mRNA leader region, which resembles the Tat-responsive element of the HIV-1 long terminal repeat (TAR) and which is therefore termed TAR-like, is essential for TNF beta transactivation by Tat. These data suggest that similar promoter regulatory elements are necessary for Tat-mediated transactivation of both TNF beta and HIV-1 gene expression. This represents the first demonstration of a cellular gene with a regulatory element downstream of the transcriptional initiation site that, like TAR, may function as an RNA element.
Buonaguro
L
L
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Buonaguro
F M
FM
Giraldo
G
G
Ensoli
B
B
D001483:Base Sequence; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000494:pharmacology*; D016356:Gene Products, tax / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016356:Gene Products, tax; D008233:Lymphotoxin-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D013755:Tetradecanoylphorbol Acetate