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  • Title: Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53.
    Author: Komiyama S, Taniguchi S, Matsumoto Y, Tsunoda E, Ohto T, Suzuki Y, Yin HL, Tomita M, Enomoto A, Morita A, Suzuki T, Ohtomo K, Hosoi Y, Suzuki N.
    Journal: Biochem Biophys Res Commun; 2004 Oct 22; 323(3):816-22. PubMed ID: 15381073.
    Abstract:
    DNA damage induces accumulation and activation of p53 via various posttranslational modifications. Among them, several lines of evidence indicated the phosphorylation of Ser46 as an important mediator of DNA damage-induced apoptosis but the responsible kinase remains to be clarified, especially in the case of ionizing radiation (IR). Here we showed that DNA-dependent protein kinase (DNA-PK) could phosphorylate Ser46 of p53 in addition to reported phosphorylation sites Ser15 and Ser37. However, IR-induced phosphorylation of Ser46 was seen even in M059J, a human glioma cell line lacking DNA-PKcs, and it was, at most, only slightly less than in control M059K. On the other hand, a related kinase ataxia-telangiectasia mutated (ATM), which was shown to be essential for IR-induced phosphorylation of Ser46, could poorly phosphorylate Ser46 by itself. These results collectively suggested two pathways for IR-induced phosphorylation of Ser46, i.e., direct phosphorylation by DNA-PK and indirect phosphorylation via ATM.
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