Abstract
Transforming growth factor-beta (TGF-beta) is implicated as a tumor suppressor because it eliminates cancer cells from normal tissues by inhibiting cell growth and inducing apoptosis. Although p53 tumor suppressor is required for TGF-beta-induced p21 WAF1 expression and cell growth inhibition, its role in TGF-beta-induced apoptosis remains unclear. Here, we report that TAp73alpha, which is a member of the p53 family, binds to p53-binding sites in the promoters of proapoptotic Bax and Puma to activate their transcription, and mediates TGF-beta-induced apoptosis in gastric cancer cells. Our findings reveal a novel role of TAp73alpha in the induction of apoptosis by TGF-beta in cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / genetics
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Apoptosis*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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E2F1 Transcription Factor / metabolism
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Humans
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / genetics
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Stomach Neoplasms / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta / pharmacology
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Tumor Protein p73
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / physiology*
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bcl-2-Associated X Protein / genetics
Substances
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Apoptosis Regulatory Proteins
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BBC3 protein, human
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DNA-Binding Proteins
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E2F1 Transcription Factor
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E2F1 protein, human
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Nuclear Proteins
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Proto-Oncogene Proteins
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Transforming Growth Factor beta
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Tumor Protein p73
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Tumor Suppressor Proteins
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bcl-2-Associated X Protein