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Trib1 is an important adaptor that connects the MAP kinase pathway with C/EBPa in leukemogenesis

Research Project

Project/Area Number 25430121
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

Yokoyama Takashi  公益財団法人がん研究会, 発がん研究部, 研究員 (00535833)

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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsTrib1 / C/EBPα / Hoxa9 / Bcl11a / 白血病 / ノックアウトマウス / ChIPシークエンス / 転写因子 / レトロウィルス挿入変異 / レトロウイルス挿入変異 / MAPキナーゼ経路
Outline of Final Research Achievements

Trib1 is a collaborator of Hoxa9/Meis1 in AML and it by itself induces AML through enhancement of MAP kinase signaling and degradation of C/EBPa. Biological phenotypes of Hoxa9-immortalized cells with different Trib1 expression status, Trib1 hi, Trib1 lo and Trib1 null, were compared. Proliferation, DNA synthesis and pERK was increased in the Trib1 hi cell. Genome-wide DNA-binding region of Hoxa9 and C/EBPa were then assessed in Trib1 hi, Trib1 lo and Trib1 null and potentially important Hoxa9 and C/EBPa target genes were searched in nearest neighbor genes of their binding peaks of which expression was 1.5-fold up- or down-regulated by Trib1 overexpression. Cdk6, Kit, Cd44, and Cd34 are such Hoxa9 target candidates up-regulated by Trib1. Also, Idh1, Tet2 and Vcam1 are down-regulated genes. These results suggested that Trib1 might alter cell cycle progression and differentiation by modulating Hoxa9-mediated transcriptional program and by repressing C/EBPa target tumor suppressor genes.

Report

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

    (11 results)

All 2016 2015 2014 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Journal Article] MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis.2016

    • Author(s)
      Yokoyama T, Nakatake M, Kuwata T, Couiznet A, Goitsuka R, Tsutsumi S, Aburatani H, Valk PJ, Delwel R, Nakamura T.
    • Journal Title

      J Clin Invest.

      Volume: 印刷中 Issue: 5 Pages: 1664-1678

    • DOI

      10.1172/jci81516

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Modulation of gene expression by Trib1, an AML disease gene and a suppressor of C/EBPa2015

    • Author(s)
      Takashi Yokoyama and Takuro Nakamura
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Meis1標的遺伝子Sytl1はCXCL12/CXCR4シグナルを介してAMLの骨髄微小環境への定着を促進する2015

    • Author(s)
      横山隆志,中武真由香,高原智子,山崎ゆかり,中村卓郎
    • Organizer
      第105回 日本病理学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] The functional role of Trib1 in normal and neoplastic hematopoiesis2015

    • Author(s)
      Takashi Yokoyama and Takuro Nakamura
    • Organizer
      Tribbles Pseudokinases on the Crossroads of Metabolism, Cancer, Immunity and Development
    • Place of Presentation
      Budapest, Hungary
    • Year and Date
      2015-04-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sytl1 promotes engraftment of Hoxa9/Meis1-induced AML in bone marrow niche b y modulating Flt3 and CXCR42014

    • Author(s)
      横山 隆志,中武 真由香,中村 卓郎
    • Organizer
      第73回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Meis1標的遺伝子Sytl1はAMLの骨髄微小環境への定着を促進する2014

    • Author(s)
      横山 隆志,中武 真由香,菅野 陽平,高原 智子,山崎 淑子,山崎 ゆかり,中村 卓郎
    • Organizer
      第103回 日本病理学会総会
    • Place of Presentation
      ANAクラウンプラザホテル広島(広島)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Sytl1/Slp1 functions in the engraftment of AML into the bone marrow

    • Author(s)
      Takashi Yokoyama, Mayuka Nakatake, Ayumi Nakamura Hidetoshi Tahara, Naoya Hatano, Takuro Nakamura
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 (横浜)
    • Related Report
      2013 Research-status Report
  • [Presentation] Trib1 AMLを利用したBcl11aによる白血病関連遺伝子制御の解析

    • Author(s)
      横山 隆志,山崎 ゆかり,菅野 陽平,高原 智子,中村 卓郎
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      さっぽろ芸文館 (札幌)
    • Related Report
      2013 Research-status Report
  • [Remarks] がん研究所 発がん研究部

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 公益財団法人がん研究会 がん研究所 発がん研究部 部門紹介

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/

    • Related Report
      2014 Research-status Report
  • [Remarks] 公益財団法人がん研究会 がん研究所 発がん研究部 部門紹介

    • URL

      http://www.jfcr.or.jp/laboratory/department/carcinogenesis/

    • Related Report
      2013 Research-status Report

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

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