Regulatory mechanism of intracellular dynamics of conformationally aberrant proteins and its pathophysiological significance

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H04022
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 48:Biomedical structure and function and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Murata Shigeo 東京大学, 大学院薬学系研究科(薬学部), 教授 (20344070)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 構造異常タンパク質 / ユビキチン / プロテアソーム / オートファジー / タウ / 神経変性疾患

Outline of Final Research Achievements

It is essential for cell survival that structurally aberrant proteins generated by environmental stresses or genetic mutations be properly degraded by intracellular protein quality control mechanisms. Furthermore, it has been known that proteins that are not fully degraded within the cell are transported to specific locations within the cell and sequestered. We have identified several novel factors involved in transporting these abnormal proteins and clarified how each factor is involved in the subcellular localization of the abnormal proteins.

Free Research Field

細胞内タンパク質分解

Academic Significance and Societal Importance of the Research Achievements

本研究により、異常タンパク質の輸送、隔離のための新たな経路と新たな分子メカニズムがあることがわかった。まだ基礎研究の段階であるが、構造異常タンパク質の発現、蓄積は、がん細胞、老化細胞、神経変性疾患における神経細胞において観察されることから、これら疾患の新規治療戦略の端緒となることが期待できる。