ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice
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Document Type
Journal ArticlePublication Date
2012-05-15Keywords
AnimalsApoptosis
Cell Cycle Proteins
*DNA Damage
DNA-Binding Proteins
Enzyme Activation
Intestine, Small
Mice
Mice, 129 Strain
Mice, Inbred C57BLMutation, MissensePhosphorylationProtein StabilityProtein-Serine-Threonine KinasesProto-Oncogene Proteins c-mdm2Radiation ToleranceSerineSpleenThymus GlandTime FactorsTumor Suppressor Protein p53Tumor Suppressor ProteinsCell and Developmental BiologyCell Biology
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DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage. In addition, we demonstrate that dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394 governs p53 protein levels and functions in cells undergoing DNA damage.Source
Cancer Cell. 2012 May 15;21(5):668-79. Link to article on publisher's siteDOI
10.1016/j.ccr.2012.04.011Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36023Related Resources
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