Development of bio-response profiling technology based on the integration of redox and phosphorylation state determination technologies

Research Project

Project/Area Number	18K14689
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 43060:System genome science-related
Research Institution	National Institute of Advanced Industrial Science and Technology
Principal Investigator	Araki Kazutaka 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (60514255)
Project Period (FY)	2018-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	翻訳後修飾 / 質量分析測定 / リン酸化 / 酸化還元 / 相互作用解析 / タンパク質 / 相互作用
Outline of Final Research Achievements	Post-translational modifications of proteins play an important role in maintaining cellular homeostasis, i.e. proteostasis. In this study, we developed a quantitative and direct analysis system to capture the crosstalk between different states of post-translational modifications of proteins: phosphorylation and oxidative modification. The quantitative analysis of the phosphorylation-modified state and the quantification of the redox state of the cysteine residues have been carried out, and at the same time, an experimental system has been successfully constructed that leads to the identification of interaction sites around the redox-reactive cysteine residues. We believe that these techniques will be a useful tool for examining signaling pathways, with a focus on crosstalk between proteins via cysteine residues.
Academic Significance and Societal Importance of the Research Achievements	活性酸素(Reactive Oxygen Species, ROS)の発生による酸化ストレスが、多岐に渡る生命現象や疾患とも密接に関わっていることに注目が集まっている。例えば、生活習慣に起因する動脈硬化や糖尿病等の疾患、加齢に伴う生体機能の低下や神経変性疾患、がん発生の原因（酸化修飾）とも密接に関与していることが知られており、その実像に迫る必要がある。特に、細胞内酸化還元状態のバランスとその制御に関して、酸化修飾とシグナル伝達という複合的な視点で、その具体的な影響をもとに両者の連関性をとらえる必要性がますます高まっており、本研究がその一助となる意義をもつ。