Controllable degradation method for proteins using a novel degradation tag

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H03289
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• 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): 2016-04-01 – 2019-03-31
• Keywords: タンパク質分解

Outline of Final Research Achievements

I previously reported that a post-translational modification of a protein is closely related to degradation of intracellular bacteria. Here, I hypothesized that this modification could work as a degradation-inducing tag also for non-bacterial targets. Various guanine derivatives were synthesized and When we introduced it into the protein and examined its effect on the protein lifespan, we found that, as expected We have discovered a derivative that shortens the protein lifetime. The mechanism of action was analyzed using various mutant cell lines related to autophagy. In addition, the generalizability of the effect was verified by increasing the number of examples of proteins subjected to degradation.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

細胞内のタンパク質レベルを低下させる分子技術は、生命科学研究において多用される遺伝学的手法と類似の効果をもたらすため、基礎医学研究の成果を創薬に結びつける手法として注目されています。特定タンパク質の分解を誘導することが主なアプローチになります。細胞内の分解機構であるUPSを使う応用は進んでいますが、オートファジーの利用は十分に進んでいませんでした。本研究は、オートファジーを細胞内の局所にリクルートする初めての分子技術を可能にしました。