Induction of nuclear NF-kappa B DNA binding activity after exposure of lymphoid cells to soluble tax1 protein.
We demonstrate that purified HTLV-I Tax1 protein can be taken up by 70Z/3 lymphoid cells and localized in both the nuclear and cytoplasmic compartments. Introduction of the Tax1 protein into the growth medium of 70Z/3 cells resulted in the rapid and transient induction of NF-kappa B binding activity in the nuclear fraction. Tax1 activation of NF-kappa B was not sensitive to either staurosporin or prolonged stimulation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, suggesting that Tax1-dependent NF-kappa B activation did not require the protein kinase C pathway. Purified Tax1 did not directly increase NF-kappa B binding activity in 70Z/3 cytoplasmic extracts, suggesting that NF-kappa B induction may require cellular factors. Western blot and competitive radioimmunoassays demonstrated that Tax1 protein was present in the tissue culture media of HTLV-I-transformed cell lines. These results show that extracellular Tax1 may regulate cellular gene expression in noninfected cells.
Lindholm
P F
PF
Laboratory of Molecular Virology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Marriott
S J
SJ
Gitlin
S D
SD
Bohan
C A
CA
Brady
J N
JN
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002472:Cell Transformation, Viral; D004247:DNA / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016356:Gene Products, tax / Q000493:pharmacokinetics / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D016356:Gene Products, tax; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011994:Recombinant Proteins; D004247:DNA; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate