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Studies on the tissue-specific role of the ubiquitin ligase UBR4 and its basic mechanisms

Research Project

Project/Area Number 18K06119
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionKanazawa Medical University

Principal Investigator

TASAKI Takafumi  金沢医科大学, 総合医学研究所, 准教授 (70629815)

Co-Investigator(Kenkyū-buntansha) 佐々木 宣哉  北里大学, 獣医学部, 教授 (20302614)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords大腸炎関連大腸がんモデル / ユビキチンリガーゼ / UBR4 / DSS/AOM大腸炎関連大腸がんモデル / 網羅的遺伝子発現解析 / 腸管上皮特異的ノックアウトマウス / DSS誘導大腸炎モデル / 翻訳後修飾 / ユビキチンリガーぜ / N-end rule pathway / 病態モデル / 組織特異的ノックアウトマウス
Outline of Final Research Achievements

The aim of this study was to elucidate the physiological role of the ubiquitin ligase UBR4 in the adult body, particularly in pathological models. Mice lacking the intestinal epithelial-specific UBR4 gene (UBR4(-)) showed properties similar to wild-type mice (UBR4(+)), but in the colitis-associated colorectal cancer model by AOM/DSS, there was a trend toward exacerbated colitis in the UBR4(-) group. In addition, the incidence of colorectal cancer after long-term rearing showed an increased incidence and number of tumors in the UBR4(-) group compared to the UBR4(+) group. These findings suggest that UBR4 has an inhibitory role in colitis and colorectal cancer development.

Academic Significance and Societal Importance of the Research Achievements

AOM/DSSによる大腸炎関連大腸がん発症は、ヒトの大腸がん発症に近いモデルと考えられている。本研究によって、腸上皮特異的UBR4欠損マウスが新たな大腸炎関連大腸がんモデルマウスとなる可能性を示した。今後、このモデルマウスを用いて大腸炎及び大腸がん発症メカニズムにおけるUBR4の役割を解明することにより、UBR4は新規薬剤ターゲットとなりえる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report

Research Products

(7 results)

All 2022 2021 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony2022

    • Author(s)
      Hegazi Sara、Cheng Arthur H.、Krupp Joshua J.、Tasaki Takafumi、Liu Jiashu、Szulc Daniel A.、Ling Harrod H.、Rios Garcia Julian、Seecharran Shavanie、Basiri Tayebeh、Amiri Mehdi、Anwar Zobia、Ahmad Safa、Nayal Kamar、Sonenberg Nahum、Liu Bao-Hua、Cheng Hai-Ling Margaret、Levine Joel D.、Cheng Hai-Ying Mary
    • Journal Title

      Nature Communications

      Volume: 13 Pages: 1594

    • DOI

      10.1038/s41467-022-29244-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The N-recognin UBR4 of the N-end rule pathway is required for neurogenesis and homeostasis of cell surface proteins2018

    • Author(s)
      Kim Sung Tae、Lee Yoon Jee、Tasaki Takafumi、Hwang Joonsung、Kang Min Jueng、Yi Eugene C.、Kim Bo Yeon、Kwon Yong Tae
    • Journal Title

      PLOS ONE

      Volume: 13 Pages: e0202260

    • DOI

      https://doi.org/10.1371/journal.pone.0202260

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the biogenesis of the early endosome2018

    • Author(s)
      Kim Sung Tae、Lee Yoon Jee、Tasaki Takafumi、Mun Su Ran、Hwang Joonsung、Kang Min Jueng、Ganipisetti Srinivasrao、Yi Eugene C.、Kim Bo Yeon、Kwon Yong Tae
    • Journal Title

      Journal of Cell Science

      Volume: 131 Pages: jcs217646

    • DOI

      doi:10.1242/jcs.217646

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] UBR4-HPV16E7相互作用の分子機構2021

    • Author(s)
      田崎 隆史, 佐々木 隼人, 佐々木 宣哉
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] DSS誘導大腸炎モデルにおけるユビキチンリガーゼUBR4の役割2020

    • Author(s)
      田崎隆史、佐々木隼人、佐々木宣哉
    • Organizer
      第67回日本実験動物学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] The role of N-recognin UBR4 in endosomal-lysosomal system2019

    • Author(s)
      Yoon Jee Lee, Sung Tae Kim, Joonsung Hwang, Takafumi Tasaki, Bo Yeon Kim, and Yong Tae Kwon
    • Organizer
      1st Anuual meeting of the International Society of Protein Termini, Protein Termini 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腸管上皮細胞特異的UBR4ノックアウトマウスはAOM/DSS誘導大腸炎を悪化させる2019

    • Author(s)
      田崎 隆史, 佐々木隼人, 佐々木宣哉
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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