Abstract
Phosphorylation at Ser-15 may be a critical event in the up-regulation and functional activation of p53 during cellular stress. In this report we provide evidence that the ATM-Rad3-related protein ATR regulates phosphorylation of Ser-15 in DNA-damaged cells. Overexpression of catalytically inactive ATR (ATRki) in human fibroblasts inhibited Ser-15 phosphorylation in response to gamma-irradiation and UV light. In gamma-irradiated cells, ATRki expression selectively interfered with late-phase Ser-15 phosphorylation, whereas ATRki blocked UV-induced Ser-15 phosphorylation in a time-independent manner. ATR phosphorylated p53 at Ser-15 and Ser-37 in vitro, suggesting that p53 is a target for phosphorylation by ATR in DNA-damaged cells.
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 / genetics
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Cell Cycle Proteins / metabolism*
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DNA Damage / physiology*
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DNA Damage / radiation effects
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DNA-Binding Proteins
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Doxycycline / pharmacology
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Fibroblasts
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Gamma Rays
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Humans
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K562 Cells
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Mutation
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Phosphorylation / drug effects
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Phosphorylation / radiation effects
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Precipitin Tests
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Protein Serine-Threonine Kinases*
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Proteins / metabolism
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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Serine / metabolism
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Time Factors
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Transfection
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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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Ultraviolet Rays
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Proteins
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Recombinant Fusion Proteins
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Serine
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ATM protein, human
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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Doxycycline