Drug target discovery for autoimmune diseases by using a technology creating functional mutant proteins

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: TSUNODA Shin-ichi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (90357533)
• Co-Investigator(Kenkyū-buntansha): KAMADA Haruhiko 独立行政法人医薬基盤研究所, 創薬基盤研究部, サブプロジェクトリーダー (00324509)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: TNF / TNFR2 / aminopeptidase P3

Outline of Final Research Achievements

Tumor necrosis factor-α（TNF-α）and its receptors (TNFR1 And TNFR2) play important roles for progression of autoimmune diseases. Therefore, they are considered to be promising drug targets for such diseases. However, differences of the function of TNFR1 and TNFR2, especially, the role of TNFR2 in diseases have not been understood well. In order to clear the possibility of the TNFR2 as a novel drug target, functions of TNFR2 must be well-investigated. This study aimed for clear the function of TNFR2 by using TNFR1/TNFR2 specific TNF mutants developed by our laboratory. Here, we identified a protein APP3 as a novel cytoplasmic adaptor molecule of TNFR2. We also found that APP3 played an important role for signal transduction from TNFR2 to JNK/MAP kinase pathway activation. These findings would be valuable for understanding the function of TNFR2.

Free Research Field

タンパク質工学