Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation
- Authors
- Cho S.-J.[Cho S.-J.]; Kang H.[Kang H.]; Kim M.Y.[Kim M.Y.]; Lee J.E.[Lee J.E.]; Kim S.J.[Kim S.J.]; Nam S.Y.[Nam S.Y.]; Kim J.Y.[Kim J.Y.]; Kim H.S.[Kim H.S.]; Pyo S.[Pyo S.]; Yang K.H.[Yang K.H.]
- Issue Date
- 1-Apr-2016
- Publisher
- ELSEVIER SCIENCE INC
- Citation
- INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, v.94, no.5, pp.1207 - 1218
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
- Volume
- 94
- Number
- 5
- Start Page
- 1207
- End Page
- 1218
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/37048
- DOI
- 10.1016/j.ijrobp.2016.01.008
- ISSN
- 0360-3016
- 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 Cs-137 gamma-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. (C) 2016 Elsevier Inc. All rights reserved.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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