Publication Date:
1988-09-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ballard, D W -- Bohnlein, E -- Lowenthal, J W -- Wano, Y -- Franza, B R -- Greene, W C -- New York, N.Y. -- Science. 1988 Sep 23;241(4873):1652-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2843985" target="_blank"〉PubMed〈/a〉
Keywords:
Acetyltransferases/genetics
;
Cell Line
;
Chloramphenicol O-Acetyltransferase
;
DNA-Binding Proteins/*biosynthesis/physiology
;
Deltaretrovirus/genetics/*physiology
;
*Gene Expression Regulation
;
Nuclear Proteins/*biosynthesis/physiology
;
Plasmids
;
Promoter Regions, Genetic
;
Receptors, Antigen, T-Cell/*genetics
;
Receptors, Immunologic/*genetics
;
Receptors, Interleukin-2
;
Retroviridae Proteins/*physiology
;
Tetradecanoylphorbol Acetate/pharmacology
;
Trans-Activators
;
Transcription Factors/*physiology
;
Transfection
;
Viral Proteins/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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