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Science 23 September 1988:
Vol. 241. no. 4873, pp. 1652 - 1655
DOI: 10.1126/science.2843985
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Articles

Science, Vol 241, Issue 4873, 1652-1655
Copyright © 1988 by American Association for the Advancement of Science

articles

HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene

DW Ballard, E Bohnlein, JW Lowenthal, Y Wano, BR Franza, and WC Greene

Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.

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.


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J. Biol. Chem. 271, 14584-14590
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O. J. Semmes, J. F. Barrett, C. V. Dang, and K.-T. Jeang (1996)
J. Biol. Chem. 271, 9730-9738
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Transactivation by AP-1 Is a Molecular Target of T Cell Clonal Anergy.
S.-M. Kang, B. Beverly, A.-C. Tran, K. Brorson, R. H. Schwartz, and M. J. Lenardot (1992)
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S. Ruben, P. Dillon, R Schreck, T Henkel, C. Chen, M Maher, P. Baeuerle, and C. Rosen (1991)
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Identification of HTLV-I tax trans-activator mutants exhibiting novel transcriptional phenotypes..
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A 65-kappaD subunit of active NF-kappaB is required for inhibition of NF-kappaB by I kappaB..
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Human chromosome 12 is required for elevated HIV-1 expression in human-hamster hybrid cells.
C. Hart, C. Ou, J. Galphin, J Moore, L. Bacheler, J. Wasmuth, S. Petteway Jr, and G Schochetman (1989)
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S. Cross, N. Halden, M. Lenardo, and W. Leonard (1989)
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