HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene.
Jurkat T cell lines constitutively expressing Tax, the 40-kilodalton transactivator protein of human T lymphotropic virus type I (HTLV-I), were used to investigate the mechanism by which this viral product deregulates the expression of the interleukin-2 receptor alpha gene (IL-2R alpha, Tac). Transfection of deleted forms of the IL-2R alpha promoter and in vitro DNA-binding studies revealed that a 12-base pair promoter segment, which has homology with the binding site for NF-kappa B, was required for Tax-induced activation of the IL-2R alpha promoter in vivo. An 18-base pair oligonucleotide containing this kappa B-like regulatory element proved sufficient to confer Tax inducibility upon a heterologous promoter. DNA affinity precipitation assays showed that Tax, like mitogenic stimuli, induced the expression of the 86-kilodalton cellular protein HIVEN86A, which specifically binds to the IL-2R alpha kappa B element in vitro. Furthermore, DNA/protein cross-linking studies revealed that several polypeptides interact with this sequence motif. Thus, the deregulation of IL-2R alpha gene expression encountered in HTLV-I leukemias appears to involve Tax activation of one or more cellular proteins that are normally induced by mitogens and that directly contribute to transcriptional activation of this receptor gene.
Ballard
D W
DW
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.
Böhnlein
E
E
Lowenthal
J W
JW
Wano
Y
Y
Franza
B R
BR
Greene
W C
WC
D000123:Acetyltransferases / Q000235:genetics; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D017977:Deltaretrovirus / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000502:physiology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D015375:Receptors, Interleukin-2; D012191:Retroviridae Proteins / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D014764:Viral Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D012191:Retroviridae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate