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

Research Project

Project/Area Number 25340027
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionNiigata 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
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
KeywordsBCL11B / 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 / がん抑制因子 / SWI/SNIF複合体 / グリセロール密度勾配遠心法 / DNAチップ解析
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.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells2015

    • Author(s)
      Takachi T, Takahashi M, Takahashi-Yoshita M, Higuchi M, Obata M, Mishima Y, Okuda S, Tanaka Y, Matsuoka M, Saitoh A, Green PL, Fujii M.
    • Journal Title

      Cance Science

      Volume: 106(4) Issue: 4 Pages: 461-465

    • DOI

      10.1111/cas.12618

    • NAID

      120006844098

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bcl11b SWI/SNF-complex subunit modulates intestinal adenoma and regeneration after γ-irradiation through Wnt/β-catenin pathway.2015

    • Author(s)
      Sakamaki A, Katsuragi Y, Otsuka K, Tomita M, Obata M, Iwasaki T, Abe M, Sato T, Ochiai M, Sakuraba Y, Aoyagi Y, Gondo Y, Sakimura K, Nakagama H, Mishima Y, Kominami R
    • Journal Title

      Carcinogenesis

      Volume: 36 Issue: 6 Pages: 622-631

    • DOI

      10.1093/carcin/bgv044

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful management of severe intrahepatic cholestasis of pregnancy: report of a first Japanese case.2014

    • Author(s)
      Kamimura K, Abe H, Kamimura N, Yamaguchi M, Mamizu M, Ogi K, Takahashi Y, Mizuno K, Kamimura H, Kobayashi Y, Takeuchi M, Yoshida K, Yamada K, Enomoto T, Takakuwa K, Nomoto M, Obata M, Katsuragi Y, Mishima Y, Kominami R, Kamimura T, Aoyagi Y.
    • Journal Title

      BMC Gastroenterol.

      Volume: 14 Issue: 1 Pages: 160-4

    • DOI

      10.1186/1471-230x-14-160

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell of origin in radiation-induced premalignant thymocytes in mice conditionally losing one Bcl11b allele.2013

    • Author(s)
      Go R, Hirose S, Katsuragi Y, Obata M, Abe M, Mishima Y, Sakimura K, Kominami R.
    • Journal Title

      Cancer Science

      Volume: 104 Issue: 8 Pages: 1009-1016

    • DOI

      10.1111/cas.12193

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bcl11b transcription factor plays a role in the maintenance of the ameloblast-progenitors in mouse adult maxillary incisors.2013

    • Author(s)
      Katsuragi Y, Anraku J, Nakatomi M, Ida-Yonemochi H, Obata M, Mishima Y, Sakuraba Y, Gondo Y, Kodama Y, Nishikawa A, Takagi R, Ohshima H, Kominami R.
    • Journal Title

      Mechanism and Development

      Volume: 130 Issue: 9-10 Pages: 482-492

    • DOI

      10.1016/j.mod.2013.05.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Role of BCL11B in the SWI/SNF chromatin remodeling complexes2014

    • Author(s)
      小幡 美貴 ・ 木南 凌・ 三嶋 行雄
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Effect of mutations in BCL11B on the SWI/SNF chromatin remodeling complexes2014

    • Author(s)
      小幡 美貴 ・ 木南 凌 ・葛城 美徳 ・ 三嶋 行雄
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 転写因子BCL11Bはp53を介して細胞周期を調節する?2013

    • Author(s)
      小幡 美貴 ・ 木南 凌 ・ 三嶋 行雄
    • Organizer
      第56回日本放射線影響学会大会
    • Place of Presentation
      ホテルクラウンパレス青森 (青森市)
    • Related Report
      2013 Research-status Report
  • [Presentation] BCL11B mutations identified in T-ALL leukemias negatively or positively affect the activity of SWI/SNF chromatin remodeling complexes2013

    • Author(s)
      小幡 美貴 ・ 木南 凌 ・ 三嶋 行雄
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド (神戸市)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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