Abstract
The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins
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Cell Line
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DNA Damage
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DNA-Activated Protein Kinase
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DNA-Binding Proteins*
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Enzyme Activation
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Humans
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Lymphocytes / metabolism
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Lymphocytes / radiation effects
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Mutation
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Nuclear Proteins
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Phosphoserine / metabolism
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Proteins / genetics
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Proteins / metabolism*
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Radiation, Ionizing*
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / metabolism
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Signal Transduction
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Transfection
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins
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Ultraviolet Rays
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Nuclear Proteins
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Proteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Phosphoserine
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Protein Kinases
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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DNA-Activated Protein Kinase
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PRKDC protein, human
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Protein Serine-Threonine Kinases