Autophagic degradation of pathogenic components by the AUTAC method

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H02844
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Tohoku University
• Principal Investigator: Arimoto Hirokazu 東北大学, 生命科学研究科, 教授 (60262789)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: オートファジー

Outline of Final Research Achievements

The materials that make up our bodies need to be properly renewed. The accumulation of harmful substances has been pointed out to lead to disease when the life span of the cell itself is long, such as in the case of nerve cells. Therefore, we studied a method to remove disease-causing substances in cells by using autophagy, a major degradation mechanism in cells. To select disease-causing substances, appropriate compounds called targeting ligands were selected, and the degradation tag structure, which was found separately, was joined with a molecular chain (linker) to form a chimeric molecule. Using this chimeric molecule: AUTAC, we achieved degradation of various proteins and mitochondria.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

オートファジーの機構解明についてノーベル賞が与えられた現在でも理解が難しい問題が残されている。そのひとつは、分解する相手（基質）を選択する機構である。私たちは、分解選択性の目印として働くタンパク質修飾を自ら見出して、これを疾患原因となるタンパク質等に自在に導入する手法：AUTAC法を開発した。特定の基質を分解する医薬品につながると期待される。オートファジー機構を用いる基質選択的分解剤は、AUTACが世界初の例であり学術的な意義も高い。