Elucidation of physiological and pathophysiological roles of Parafibromin tyrosine phosphorylation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16734
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kikuchi Ippei 東京大学, 大学院医学系研究科(医学部), 特任研究員 (80772376)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: がん / シグナル伝達 / リン酸化 / ゲノム編集

Outline of Final Research Achievements

In this study, we aimed to elucidate physiological and pathophysiological roles of Parafibromin, which integrates multiple cancer-related signaling pathways. To do so, here we generated the Ptk6 family kinase multiple knockout mice by using CRISPR/Cas system-mediated genome editing. Analyses of the newly generated mice revealed that Parafibromin tyrosine phosphorylation by Ptk6 family kinases plays a critical role in regulating intestinal tissue homeostasis. Furthermore, our results indicated that it may also contribute to the development of human intestinal diseases such as inflammatory bowel disease (IBD) and radiation-induced gastrointestinal syndrome.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、Ptk6ファミリーキナーゼによるParafibrominのチロシンリン酸化制御は腸管上皮の組織恒常性維持に働くことが示され、さらには炎症性腸疾患や放射線誘導性消化管症候群といった臨床的に重要な意義を持つ疾患の発症に役割を担うことが示された。この成果を足掛かりに、今後はParafibrominのチロシンリン酸化を制御可能な薬剤などをスクリーニングすることで、それらの難治性の疾患に対する新たな治療法の開発につながることが期待できる。