The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV.
Both the interleukin-2 receptor-alpha (Tac, p55, IL-2R alpha) gene and the long terminal repeat (LTR) of type 1 HIV are activated by various T cell mitogens. We now demonstrate that an inducible 86 kd nuclear protein termed HIVEN86A specifically binds to both the enhancer element of the HIV-1 LTR and a closely related 12 bp sequence present in the 5' regulatory region (-267 to -256) of the IL-2R alpha gene. The interaction of these binding sites with HIVEN86A and perhaps other cellular proteins such as NF-kappa B appears importantly involved in mitogen activation since the isolated IL-2R alpha promoter binding site or single elements of the normally duplicated HIV-1 enhancer alone are sufficient to confer mitogen inducibility on an unresponsive heterologous promoter. Together these findings suggest that the normal action of an inducible nuclear DNA binding protein(s) involved in the regulation of IL-2R alpha gene expression can be subverted by the HIV-1 provirus to promote activation of retroviral gene transcription.
Böhnlein
E
E
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Lowenthal
J W
JW
Siekevitz
M
M
Ballard
D W
DW
Franza
B R
BR
Greene
W C
WC
D001483:Base Sequence; D002460:Cell Line; D004262:DNA Restriction Enzymes; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes; D005800:Genes, Fungal; D005809:Genes, Regulator; D006678:HIV / Q000235:genetics*; D007376:Interleukin-2 / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D015375:Receptors, Interleukin-2; D012689:Sequence Homology, Nucleic Acid
D007376:Interleukin-2; D008934:Mitogens; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D004262:DNA Restriction Enzymes