The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c-rel proto-oncogene.
The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor (IL-2R alpha) via a kappa B site that can bind several protein species of the rel family. Tax1 strongly activates the enhancer activity of this motif, in both epithelial HeLa and lymphoid Jurkat cells. This activation was not observed in undifferentiated embryocarcinoma F9 cells. Overexpression of the p50, p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65. Moreover, whereas both Tax and phorbol 12-myristate 13-acetate (PMA) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site, PMA is functionally inactive. Using the DNA affinity precipitation assay, we observed that Tax1 is able to efficiently induce the binding of Rel, whereas PMA is not. This established a clear difference between both stimuli, indicating that Rel is the functionally active factor. We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites.
Crenon
I
I
Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure de Lyon, France.
Béraud
C
C
Simard
P
P
Montagne
J
J
Veschambre
P
P
Jalinot
P
P
D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020569:Proto-Oncogene Proteins c-rel; D011519:Proto-Oncogenes; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D016356:Gene Products, tax; C000715470:MAS1 protein, human; D046911:Macromolecular Substances; D016328:NF-kappa B; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate