Comprehensive analysis of O-GlcNAcylated proteins using soluble GalNAc-transferase

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03639
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Yamamoto Kazuo 東京大学, 大学院新領域創成科学研究科, 教授 (20174782)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 糖鎖 / 翻訳後修飾 / 糖転移酵素

Outline of Final Research Achievements

It is well known that O-GlcNAcylation of nuclear and cytoplasmic proteins, such as transcription factors, induces differentiation and proliferation of the cell and furthermore, such modification regulates their proteostasis. We noticed that O-GlcNAcylation of proteins plays an important role in their functions, however there are many difficulties in their biochemical and biological analyses. In this project, we established many kinds of analytical methods to clarify the meaning of O-GlcNAc modification of proteins through high sensitive identification of O-GlcNAcylated proteins, identification of GlcNAc-modified residues, establishment of antibodies specific for GlcNAc-modified residues, observation of dynamic protein modification by O-GlcNAc, and identification interacting partner protein with O-GlcNAcylated proteins.

Free Research Field

糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

タンパク質の機能を制御する薬剤が多数作られることにより、さまざまな病気を治療し改善することが可能となっているが、核内・細胞質内のO-GlcNAc修飾を標的とした創薬は未だに何一つ行われていない。多くの創薬標的分子に関して、さまざまな薬剤の開発が試みられているように、今回の研究の対象とした核内・細胞質内タンパク質のO-GlcNAc修飾が新たな創薬標的分子の一つの大きな対象となりうることを示し、そのアプローチの道筋を開いた成果と考える。