Abstract
The tumor suppressor p53 is activated by phosphorylation and/or acetylation. We constructed 14 non-phosphorylated, 11 phospho-mimetic, and 1 non-acetylated point p53 mutations and compared their transactivation ability in U-87 human glioblastoma cells by the luciferase reporter assay. Despite mutations at the phosphorylation sites, only the p53-K120R and p53-S9E mutants had marginally reduced activities. On the other hand, the Nuclear factor of activated T-cells (NFAT)-luciferase reporter was more potently activated by p53-K120R than by wild-type p53 and other mutants in glioblastoma, hepatoma and esophageal carcinoma cells. This suggests that acetylation at Lys-120 of p53 negatively regulates a signaling pathway leading to NFAT activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Binding Sites / genetics
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism
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Cell Line, Tumor
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Esophageal Neoplasms / genetics
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Esophageal Neoplasms / metabolism
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Genes, Reporter
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Glioblastoma / genetics
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Glioblastoma / metabolism
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Humans
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Luciferases / genetics
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Lysine / chemistry
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Mutagenesis, Site-Directed
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NFATC Transcription Factors / genetics
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NFATC Transcription Factors / metabolism*
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Phosphorylation
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Point Mutation
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Proline Oxidase / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / metabolism
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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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Signal Transduction
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Transcriptional Activation
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Transfection
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Tumor Suppressor Protein p53 / chemistry
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism*
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Urinary Bladder Neoplasms / genetics
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Urinary Bladder Neoplasms / metabolism
Substances
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NFATC Transcription Factors
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RNA, Messenger
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RNA, Neoplasm
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Recombinant Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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Luciferases
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Proline Oxidase
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Lysine