Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53.
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.
Komiyama
Shingo
S
Department of Radiation Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Taniguchi
Sachiko
S
Matsumoto
Yoshihisa
Y
Tsunoda
Eri
E
Ohto
Takayo
T
Suzuki
Yuka
Y
Yin
Hong-Lan
HL
Tomita
Masanori
M
Enomoto
Atsushi
A
Morita
Akinori
A
Suzuki
Takahiko
T
Ohtomo
Kuni
K
Hosoi
Yoshio
Y
Suzuki
Norio
N
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*
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