Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53

Biochemical and Biophysical Research Communications
Shingo KomiyamaNorio Suzuki

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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Citations

Dec 23, 2004·Science's STKE : Signal Transduction Knowledge Environment·Galit Lahav
Dec 17, 2015·Journal of Radiation Research·Mukesh Kumar SharmaYoshihisa Matsumoto
Sep 28, 2014·Journal of Experimental & Clinical Cancer Research : CR·Alessia Garufi, Gabriella D'Orazi
Dec 22, 2009·Journal of Biochemical and Molecular Toxicology·Sridevi YadavilliPerpetua M Muganda
May 4, 2005·Biochemical and Biophysical Research Communications·Kristina ViktorssonRolf Lewensohn
Sep 25, 2018·Journal of Radiation Research·Ali Reza Amiri MoghaniYoshihisa Matsumoto
Aug 23, 2020·Cells·Andrey AnisenkoMarina Gottikh
Jun 2, 2005·International Journal of Cancer. Journal International Du Cancer·Jing AnPing-Kun Zhou

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