Intracellular delivery of p53 fused to the basic domain of HIV-1 Tat.

p53 is a potent tumor suppressor inactivated in many cancers. In this study, the membrane permeability of the HIV-1 Tat basic domain was exploited to introduce functional p53 into cancer cells. We expressed and purified a p53 fusion protein with the HIV-1 Tat basic domain at its N terminus (Tat-p53), and examined its transduction profile and biological activity in cancer cells. Tat-p53 was efficiently delivered to both the cytoplasm and nucleus of cells, and was transcriptionally active, as judged by the level of p21/WAF1 protein and of p21 promoter activity. Transduction of cells with Tat-p53 resulted in apoptotic cell death in both p53 positive and negative human tumor cell lines. These results suggest that Tat-p53 could be useful in cancer therapy.