Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology
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Cell Survival
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / metabolism
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Enzyme Inhibitors / metabolism
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Gene Products, tat / metabolism*
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Gene Transfer Techniques
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Genes, p53*
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Genetic Vectors / genetics
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Genetic Vectors / metabolism
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HIV-1 / genetics
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HIV-1 / metabolism*
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Humans
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism*
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Transduction, Genetic*
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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tat Gene Products, Human Immunodeficiency Virus
Substances
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Gene Products, tat
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Recombinant Fusion Proteins
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Tumor Suppressor Protein p53
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tat Gene Products, Human Immunodeficiency Virus