Effect of BCL11B and its mutations on the radiation response: analysis of a p53-MDM2 feed-back loop

2015 Fiscal Year Final Research Report

• Project/Area Number: 25340027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Niigata University
• Principal Investigator: OBATA Miki 新潟大学, 医学部, 教務職員 (00420307)
• Co-Investigator(Kenkyū-buntansha): MISHIMA Yukio 新潟大学, 医歯学系, 准教授 (30142029) ; KOMINAMI Ryo 新潟大学, 医歯学総合研究科, 研究員 (40133615) ; KATSURAGI Yoshinori 新潟大学, 医歯学系, 助教 (60401759)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: BCL11B / がん抑制遺伝子 / SWI/SNF複合体 / 放射線応答 / p53-MDM2フィードバックループ

Outline of Final Research Achievements

Comprehensive profiling of cancer genomics has revealed that somatic mutations of genes encoding SWI/SNF chromatin complexes are a common driver mechanism of tumorigenesis. Since BCL11B was reported to affect transcription as a SWI/SNF component, we examined whether BCL11B incorporated into SWI/SNF complexes in HCT116 cells by transfecting BCL11B expression plasmids into cells, followed by glycerol density sedimentation analysis of the cell lysates. Most of the wild-type BCL11B but not the mutant-type BCL11B proteins were detected in the fractions of large complexes with BRG1 and other SWI/SNF components, indicating that BCL11B is the subunit of SWI/SNF complexes. Initially, we attempted to investigate whether the mutation of BCL11B affects the oscillation of p53-MDM2 by gamma ray irradiation. We failed to detect the difference of oscillation of p53-MDM2 between in the presence of wild-type and mutant-type BCL11B.

Free Research Field

分子生物学