Abstract
Human papillomavirus (HPV) is the major cause of cervical cancer worldwide. HPV-E6 protein targets the p53 tumor suppressor protein for degradation by ubiquitin-mediated proteolysis making such cancers resistant to p53-gene therapy. Here we show that infection of human cancer cells by E6-expressing adenovirus (Ad-E6) leads to degradation of both wild-type or mutant p53 protein. Interestingly, the p53-homologue candidate tumor suppressor p73 is not degraded in Ad-E6 infected cancer cells. Wild-type p73beta and not wild-type p53 or mutant p73 is a potent inhibitor of cancer colony growth and inducer of apoptosis, despite HPV-E6 overexpression. The results suggest a novel strategy using p73beta in gene therapy of HPV-E6 expressing cancers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis*
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DNA-Binding Proteins / physiology*
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Genes, Tumor Suppressor*
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Humans
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Ligases / metabolism
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Nuclear Proteins / physiology*
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Oncogene Proteins, Viral / metabolism
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Papillomaviridae*
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Papillomavirus Infections / pathology
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Papillomavirus Infections / virology*
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Protein Binding
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Repressor Proteins*
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Tumor Cells, Cultured
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Tumor Protein p73
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Tumor Suppressor Protein p53 / physiology*
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Tumor Suppressor Proteins
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Tumor Virus Infections / pathology
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Tumor Virus Infections / virology*
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Ubiquitin-Protein Ligases
Substances
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DNA-Binding Proteins
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E6 protein, Human papillomavirus type 16
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E6 protein, Human papillomavirus type 18
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Nuclear Proteins
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Oncogene Proteins, Viral
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Repressor Proteins
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TP73 protein, human
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Tumor Protein p73
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases
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Ligases