Abstract
The p53 tumor suppressor plays a major role in preventing tumor development by transactivating genes to remove or repair potentially tumorigenic cells. Here we show that the Y-box-binding protein, YB1, acts as a negative regulator of p53. Using reporter assays we show that YB1 represses transcription of the p53 promoter in a sequence-specific manner. We also show that YB1 reduces endogenous levels of p53, which in turn reduces p53 activity. Conversely, inhibiting YB1 in a variety of tumor cell lines induces p53 activity, resulting in significant apoptosis via a p53-dependent pathway. These data suggest that YB1 may, in some situations, protect cells from p53-mediated apoptosis, indicating that YB1 may be a good target for the development of new therapeutics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / physiology*
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CCAAT-Enhancer-Binding Proteins / physiology*
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Cloning, Molecular
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / physiology
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Gene Expression Regulation / physiology*
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Genes, p53 / genetics*
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Humans
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NFI Transcription Factors
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Nuclear Proteins
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Promoter Regions, Genetic
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Rats
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Recombinant Proteins / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / physiology
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Transcription Factors / genetics*
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Transcription Factors / physiology
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
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Y-Box-Binding Protein 1
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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NFI Transcription Factors
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Nuclear Proteins
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Recombinant Proteins
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Repressor Proteins
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Transcription Factors
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Y-Box-Binding Protein 1
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YBX1 protein, human
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Ybx1 protein, rat