Roles of DYRK2 Kinase in Controlling Development via Primary Cilia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: YOSHIDA SAISHU 東京慈恵会医科大学, 医学部, 講師 (40772744)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Hedgehogシグナル / 一次繊毛 / GLI2/GLI3 / DYRK2 / 髄芽腫 / 基底細胞がん

Outline of Final Research Achievements

Understanding the control mechanisms of tissue development not only contributes to the comprehension of developmental disorders but also to the understanding of tumor formation. In this study, we conducted functional analysis of Dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2), a newly identified developmental-related molecule localized to primary cilia. Omics analyses, including interactome, revealed that DYRK2 acts as a "positive regulator" in the control mechanism of Hedgehog signaling activation, thereby elucidating critical gaps of the Hedgehog signaling.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

Hedgehogシグナルの異常活性は、奇形疾患だけでなく、髄芽腫や基底細胞がんをはじめとする腫瘍形成を促進する。本研究から、これまでブラックボックスであったSmoothened (SMO)下流のHedgehogシグナル活性化機構とその責任分子(DYRK2)を同定した。本研究成果をもとに、現行のHedgehog阻害薬 (Vismodegib/Sonidegib)とは作用点の異なる、新たな創薬シーズの開発へ応用が可能である。