F. Demarchi et al., ACTIVATION OF TRANSCRIPTION FACTOR NF-KAPPA-B BY THE TAT PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, Journal of virology, 70(7), 1996, pp. 4427-4437
A recombinant Tar protein was used to investigate the molecular mechan
isms of transcriptional activation of the human immunodeficiency virus
type 1 long terminal repeat (LTR). Liposome-mediated delivery of this
protein to responsive cells results in dose-dependent LTR activation.
As evaluated by mRNA quantitation with competitive PCR, the activatio
n response is rapid and transient, peaking at 5 h after the beginning
of Tat treatment. In vivo footprinting experiments at the LTR shelved
that transcriptional activation is concomitant with a modification of
the protein-DNA interaction pattern at the downstream kappa B Site of
the enhancer and at the adjacent Spl boxes. The effects of Tar on the
enhancer are mediated by Tat-induced nuclear translocation of NF-kappa
B, which parallels the kinetics of transcriptional activation. This i
nduction results from degradation of the inhibitor I kappa B-alpha, is
blocked under antioxidant conditions and by a protease inhibitor, and
occurs as a rapid response in different cell types. The functional re
sponse to Tat is impaired upon cell treatment with a kappa B site deco
y or with sodium salicylate, an inhibitor of NF-kappa B activation, Th
ese results show that NF-kappa B activation by Tat is important for LT
R transcriptional activation. Furthermore, they suggest that some of t
he pleiotropic effects of Tat on cellular functions can be mediated by
induction of NF-kappa B.