The analysis of non-apoptotic caspase activity by TurboID-mediated proximal labeling

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16137
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Shinoda Natsuki 東京大学, 大学院薬学系研究科(薬学部), 助教 (30838397)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: カスパーゼ / 非細胞死性の機能 / TurboID / 近接依存性標識法 / ショウジョウバエ

Outline of Final Research Achievements

I have previously found that among the Caspase-3 family proteins, Drice and Dcp-1, only Dcp-1 regulates Drosophila wing size in a non-apoptotic manner. In this study, I found that cleavage of Acinus, a substrate specific for Dcp-1, is important for the regulation of wing size. In addition, by using TurboID-mediated proximity labeling, I found that proteins in proximal to Drice and Dcp-1 are different from each other. Furthermore, I found that Drice and Dcp-1 differ in their ability to induce cell death upon overexpression. These results indicate the existence of a mechanism by which Caspase-3 family proteins are used in different ways in both apoptotic and non-apoptotic processes.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

細胞死実行因子として有名なカスパーゼは, 細胞死を超えてその他多くの生理機能を発揮する. しかし, なぜカスパーゼが細胞死を回避しながら, その他の生理機能を発揮することができるのか, その分子機構の理解は未だ不十分である. 本研究から, 同一のアミノ酸配列 (典型的にはDEVD↓G) を切断するCaspase-3ファミリータンパク質DriceとDcp-1の細胞文脈に応じた使い分けが, 細胞死を回避しながら, その他の生理機能の発揮を可能にする分子機構の一端であることが提示された. 提示された概念は, その他のカスパーゼの非細胞死性の機能の分子機構の理解を進めうるものである.