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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kanazawa 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
• Keywords: 大腸炎関連大腸がんモデル / ユビキチンリガーゼ / UBR4

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.

Free Research Field

ユビキチン・プロテアソームタンパク質分解システム

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。