Abstract
The ATM protein, encoded by the gene responsible for the human genetic disorder ataxia telangiectasia (A-T), regulates several cellular responses to DNA breaks. ATM shares a phosphoinositide 3-kinase-related domain with several proteins, some of them protein kinases. A wortmannin-sensitive protein kinase activity was associated with endogenous or recombinant ATM and was abolished by structural ATM mutations. In vitro substrates included the translation repressor PHAS-I and the p53 protein. ATM phosphorylated p53 in vitro on a single residue, serine-15, which is phosphorylated in vivo in response to DNA damage. This activity was markedly enhanced within minutes after treatment of cells with a radiomimetic drug; the total amount of ATM remained unchanged. Various damage-induced responses may be activated by enhancement of the protein kinase activity of ATM.
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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Adaptor Proteins, Signal Transducing
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Androstadienes / pharmacology
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Ataxia Telangiectasia / metabolism
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Ataxia Telangiectasia Mutated Proteins
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Carrier 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-Binding Proteins
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Enzyme Inhibitors / pharmacology
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Humans
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Mutation
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Phosphatidylinositol 3-Kinases / chemistry
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Kinase Inhibitors
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Protein Kinases / chemistry
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases*
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Proteins / antagonists & inhibitors
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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Recombinant Proteins / metabolism
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins
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Wortmannin
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Zinostatin / pharmacology
Substances
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Adaptor Proteins, Signal Transducing
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Androstadienes
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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EIF4EBP1 protein, human
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Enzyme Inhibitors
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Phosphoproteins
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Protein Kinase Inhibitors
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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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Zinostatin
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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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Protein Serine-Threonine Kinases
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Wortmannin