Life and disease orchestrated by lipid metabolizing enzymes

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H04012
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Yamagata University
• Principal Investigator: Goto Kaoru 山形大学, 医学部, 教授 (30234975)
• Co-Investigator(Kenkyū-buntansha): 中野 知之 山形大学, 医学部, 准教授 (00333948) ; 田中 俊昭 山形大学, 医学部, 助教 (70536987)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脂質代謝 / ジアシルグリセロールキナーゼ / 転写調節 / 酵素活性 / p53 / NF-kB

Outline of Final Research Achievements

Major constituents of lipid bilayer, phospholipids, are initially produced by phosphorylation of diacylglycerol (DG). We are working on the functional analysis of DG-phosphorylating enzyme, DG kinase (DGK). In this study, we investigated regulatory mechanisms of tumor suppressor p53 and master transcription factor of inflammation NF-kB by DGKzeta and its binding partners. We found that DGKzeta enzymatic activity positively regulates p53 transcription activity whereas it negatively regulates NF-kB transcription activity. In addition, DGKzeta binding partners modulate specificity and selectivity of these transcription factors. These results suggest that DGKzeta plays an important role in the regulation of transcription factors through the enzymatic activity.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

三大栄養素の一つである脂質は、貯蔵エネルギーとしてのみならず、生命の基本単位である細胞の外壁（細胞膜）の構成要素としても機能する。細胞膜の脂質はさらに、その合成や分解の過程において、細胞機能を調節する情報伝達物質の役割も果たす。本研究では、代表的な脂質の一つであるジアシルグリセロールの代謝酵素が、その活性を利用して、細胞核内の遺伝子転写機構を調節することを明らかにした。