Abstract
Previous work has established that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is stabilized in an ATM-dependent manner in response to DNA damage and acts as a cofactor for p53-mediated transcription. Here, we show that in response to DNA damage caused by ionizing radiation, hnRNP K is phosphorylated in an ATM-dependent manner. Furthermore, our data indicate that ATM-dependent hnRNP K phosphorylation is required for its stabilization and its function as a p53 transcriptional cofactor in response to DNA damage. These findings thereby establish hnRNP K as an ATM target and help define how ATM orchestrates p53-dependent transcriptional responses in response to genotoxic stress.
Keywords:
ATM; DNA damage; p53; phosphorylation; transcription.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle / genetics
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Cell Cycle / radiation effects
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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DNA Damage*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Gamma Rays
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Heterogeneous-Nuclear Ribonucleoprotein K / genetics*
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Heterogeneous-Nuclear Ribonucleoprotein K / metabolism
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Humans
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction / radiation effects
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Transcription, Genetic / radiation effects
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Transcriptional Activation / radiation effects*
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Tumor Suppressor Protein p53 / agonists
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Tumor Suppressor Protein p53 / genetics*
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism
Substances
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Cell Cycle Proteins
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DNA-Binding Proteins
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Heterogeneous-Nuclear Ribonucleoprotein K
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases