title: Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53.
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.
authors.affiliation: Department of Radiation Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Komiyama
authors.forename: Sachiko
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Eri
authors.initials: E
authors.lastname: Tsunoda
authors.forename: Takayo
authors.initials: T
authors.lastname: Ohto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hong-Lan
authors.initials: HL
authors.lastname: Yin
authors.forename: Masanori
authors.initials: M
authors.lastname: Tomita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Akinori
authors.initials: A
authors.lastname: Morita
authors.forename: Takahiko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kuni
authors.initials: K
authors.lastname: Ohtomo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hosoi
authors.forename: Norio
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor / Q000201:enzymology / Q000528:radiation effects; D004247:DNA / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins; D010766:Phosphorylation / Q000528:radiation effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D012694:Serine; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases