Control of transcription factors and epigenetic factors via nuclear transport and its application to targeted therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26280108
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Nihon University
• Principal Investigator: KANEKO Hiroki 日本大学, 文理学部, 上席研究員 (10349946)
• Co-Investigator(Renkei-kenkyūsha): YONEDA Yoshihiro 医療基盤・健康・栄養研究所, 研究所長 (80191667) ; YASUHARA Noriko 日本大学, 文理学部, 准教授 (90423152) ; KONDOU Yutaka 名古屋大学, 大学院医学系研究科, 教授 (00419897) ; OKUZAKI Daisuke 大阪大学, 微生物病研究所, 助教 (00346131)
• Research Collaborator: YAMAGISHI Ryosuke ; SHIMADA Jiro
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 核輸送 / 生体生命情報学 / 発現制御 / インポーチン / 転写因子 / エピジェネティクス / 計算構造生物学 / NLS

Outline of Final Research Achievements

To contribute to the elucidation of nuclear transport mechanisms we have (1) predicted the structure of the complex formed between transcription factor Oct3/4 and importin α; (2) performed a comprehensive analysis of the dynamic structure of nuclear localization signals (NLS); and (3) elucidated the release mechanism of cargo proteins from importin α. In addition, we identified two NLS sites in epigenetic factor EZH2 and inferred its nuclear import mechanism. Furthermore, we designed and developed chemical compounds that inhibit the formation of the PRC2 complex including EZH2 and then explored their potential for the targeted therapy of lymphomas and other cancers.

Free Research Field

計算構造生物学　生体生命情報学