Abstract
It is well established that adenovirus E1B-55K protein functions as an inhibitor of the tumor suppressor protein p53 by binding and inactivating p53 as a transcriptional activator protein. Here we show that the adenovirus 2 E1B-55K protein also blocks p53 as a transcriptional repressor protein of the survivin and the MAP4 promoters. The repression is dependent on the ability of E1B-55K to bind to p53 and is enhanced by coexpression of the adenovirus E4orf6 protein. Overexpression of the transcriptional corepressor protein Sin3A partially relieves the inhibitory effect of E1B-55K, suggesting that E1B-55K blocks p53 functions by interfering with the Sin3 complex.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenovirus E1B Proteins / chemistry
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Adenovirus E1B Proteins / genetics
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Adenovirus E1B Proteins / metabolism*
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Adenovirus E4 Proteins / genetics
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Adenovirus E4 Proteins / metabolism
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Adenoviruses, Human / genetics
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Adenoviruses, Human / metabolism*
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Cell Line
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Humans
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In Vitro Techniques
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins / genetics*
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Neoplasm Proteins
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Open Reading Frames
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Promoter Regions, Genetic
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Protein Binding
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sin3 Histone Deacetylase and Corepressor Complex
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Survivin
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Transcription, Genetic
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Adenovirus E1B Proteins
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Adenovirus E4 Proteins
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Recombinant Proteins
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Repressor Proteins
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SIN3A transcription factor
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Survivin
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Tumor Suppressor Protein p53
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Sin3 Histone Deacetylase and Corepressor Complex