Regulation of cellular function by intracellular/intranuclear amino acids

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19555
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Osaka University
• Principal Investigator: Morii Eiichi 大阪大学, 医学系研究科, 教授 (10283772)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 腫瘍 / 遺伝子発現 / 腫瘍代謝

Outline of Final Research Achievements

We revealed that various amino acids regulated cellular function especially in gene expression. Here, we evaluated the function of serine racemase, which converts D-from to L-form of serine. We found that serine racemase was highly expressed in colon adenocarcinoma as compared to adjacent normal colon mucosa. Pyruvate, which is important in energy production, was synthesized from serine via serine racemase. In addition, serine racemase played an important role in gene expression with epigenetic manner. Through these results, we revealed that amino acids are not only component of protein or peptide but also function as a metabolite regulating cellular function especially in gene regulation.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

アミノ酸は従来、タンパク質やペプチドの構成体としてしか考えられていなかったが、それ以外にも様々な細胞機能に関与することが明らかにされつつある。本研究では、これまでアルギニン代謝が腫瘍の悪性化に重要であることを明らかにしており、さらに今回、エネルギー代謝に重要な役割を担うピルビン酸の産生にもセリンの光学異性体を変換する物質が関与することを新たに見出し、これらが遺伝子発現をも制御していることを報告した。アミノ酸の様々な機能を明らかにしており、これらは新たな腫瘍治療のターゲットとなりうる。