방사선생물학

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  • 2016년 05월호
    [Int J Radiat Oncol Biol Phys.] Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.

    방사선보건연구원/조성준, 양광희*

  • 출처
    Int J Radiat Oncol Biol Phys.
  • 등재일
    2016 Apr 1
  • 저널이슈번호
    94(5):1207-18.
  • 내용

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    Abstract

    PURPOSE:

    To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor.

     

    METHODS AND MATERIALS:

    Splenocytes and IM-9 cells were uniformly irradiated with various doses of a (137)Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed.

     

    RESULTS:

    First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression.

     

    CONCLUSION:

    Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast. 

     

    Author information

    Cho SJ1, Kang H1, Kim MY2, Lee JE1, Kim SJ1, Nam SY1, Kim JY1, Kim HS1, Pyo S3, Yang KH4.

    1KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.

    2Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan, South Korea.

    3College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.

    4KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea. Electronic address: kwangheey@khnp.co.kr. 

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