title: Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.
abstract: OBJECTIVE
  To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Seong-Jun
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan, South Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Seon Young
authors.initials: SY
authors.lastname: Nam
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea.
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
authors.affiliation: KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul, South Korea. Electronic address: kwangheey@khnp.co.kr.
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Yang
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D004247:DNA / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation / Q000235:genetics / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D059807:S Phase Cell Cycle Checkpoints / Q000502:physiology*
chemical_list: D051740:Ikaros Transcription Factor; D004247:DNA; D047390:Casein Kinase II; D051057:Proto-Oncogene Proteins c-akt