TY - JOUR
T1 - Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53
AU - Komiyama, Shingo
AU - Taniguchi, Sachiko
AU - Matsumoto, Yoshihisa
AU - Tsunoda, Eri
AU - Ohto, Takayo
AU - Suzuki, Yuka
AU - Yin, Hong Lan
AU - Tomita, Masanori
AU - Enomoto, Atsushi
AU - Morita, Akinori
AU - Suzuki, Takahiko
AU - Ohtomo, Kuni
AU - Hosoi, Yoshio
AU - Suzuki, Norio
N1 - Funding Information:
We thank Dr. Yoichi Taya (National Cancer Center Research Institute), Dr. Hirobumi Teraoka, and Dr. Kenichi Shinohara (Tokyo Medical and Dental University) for valuable comments and advices. S.K., S.T., E.T., T.O., and Y.S. were undergraduate students of Tokyo University of Pharmacy and Life Science and thank their supervisors Dr. Hideyo Yasuda, Dr. Kiyoko Fukami, and Dr. Hirofumi Tanaka. We also thank Dr. Noriko Umeda and Mr. Naoki Namba for their help at the very early stage of this study. This work was supported in part by a Grant-in-Aid for Scientific Research in Priority Areas from the Ministry of Education, Culture, Sport, Science and Technology (MEXT) of Japan (to Y.M.).
PY - 2004/10/22
Y1 - 2004/10/22
N2 - 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.
AB - 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.
KW - Ataxia-telangiectasia mutated
KW - DNA double-strand break
KW - DNA-dependent protein kinase
KW - Ionizing radiation
KW - Phosphorylation
KW - p53
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U2 - 10.1016/j.bbrc.2004.08.161
DO - 10.1016/j.bbrc.2004.08.161
M3 - Article
C2 - 15381073
AN - SCOPUS:4544222292
SN - 0006-291X
VL - 323
SP - 816
EP - 822
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -