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 Sp1 binding region of the HIV-1 LTR and contributes to the TNF induction of this promoter. In this study we show that the transcription factor Sp1 cooperates with p53 in the transcriptional activation directed by the HIV-1 LTR. The presence of Sp1 increased p53 binding to its recognition sequence in the HIV-1 LTR, and experiments in Drosophila cells show that Sp1 is necessary for full transactivation by mutant p53. Importantly, TNF induced the association between p53 and Sp1 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 Sp1 may play an important role in modulating certain functions of p53
