P53 AND SP1 INTERACT AND COOPERATE IN THE TUMOR NECROSIS FACTOR-INDUCED TRANSCRIPTIONAL ACTIVATION OF THE HIV-1 LONG TERMINAL REPEAT

Tumor necrosis factor alpha (TNF) is a potent activator of transcription directed by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). We have recently reported that the p53 tumor suppressor gene product binds to a site within the Spl binding region of the HIV-1 LTR and contributes to the TNF induction of this promoter. In this study Re show that the transcription factor Spl cooperates with p53 in the transcriptional activation directed by the HIV-1 LTR. The presence of Spl increased p53 binding to its recognition sequence in the HIV-1 LTR, and experiments in Drosophila cells show that Spl is necessary for full transactivation by mutant p53. Importantly, TNF induced the association between p53 and Spl in Jurkat T cells. These data demonstrate a synergistic role for these proteins in the mechanism of TNF induction of HIV-1 LTR-mediated transcription and suggest that Spl may play an important role in modulating certain functions of p53.