Regulatory mechanisms of vitamin K metabolism through GTP metabolic sensors and their application to cancer therapy.

2022 Fiscal Year Final Research Report

• Project/Area Number: 18KK0455
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Shibaura Institute of Technology
• Principal Investigator: Hirota Yoshihisa 芝浦工業大学, システム理工学部, 准教授 (70724277)
• Project Period (FY): 2019 – 2022
• Keywords: GTPセンサー / PI5P4Kβ / 糖尿病 / 健康寿命 / ビタミンK / UBIAD1

Outline of Final Research Achievements

Vitamin K has been reported to have two functions: anti-tumour and prevention of cancer recurrence, but the mechanisms of these effects are not clear. We have previously found that the vitamin K-converting enzyme UBIAD1 is regulated by GTP energy metabolism. This study aimed to "Regulatory mechanisms of vitamin K metabolism through GTP metabolic sensors and their application to cancer therapy." I came to the USA at the time of the COVID-19 outbreak worldwide, so the research plan was modified to generate F205L knock-in mice by genome editing of the GTP sensor gene and analysing the phenotype. The GTP sensor was found to affect body weight change, glucose metabolism and life span in the mice.

Free Research Field

分子栄養学

Academic Significance and Societal Importance of the Research Achievements

GTPセンサーPI5P4Kβは細胞膜脂質であるPI(5)PをPI(4,5)P2にリン酸化するキナーゼである。PI5P4Kβノックアウトマウスは、PI5P4Kβのキナーゼ活性が欠損した表現型だけでなく、他のキナーゼのスキャフォールディングタンパク質としての機能も失う。さらにATP依存性のキナーゼ活性も消失することから、GTPセンサーとしてのPI5P4Kβの生体での役割は未知である。本研究から、GPI5P4Kβは生体において、糖尿病および健康寿命に重要な役割を果たしていることが示された。今後は、PI5P4Kβを標的とした2型糖尿病やサルコペニアへの新たな治療戦略に応用できることが期待される。