Analysis of post-translational processing of the nuclear membrane protein regulating the extracellular signaling pathway

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16147
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Teikyo University
• Principal Investigator: Kobayashi Yumeko (小林夢子) 帝京大学, 先端総合研究機構, 助教 (00756447)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 核膜蛋白質 / 翻訳後修飾 / TGF-βシグナル伝達

Outline of Final Research Achievements

The inner nuclear membrane protein MAN1 functions as a negative regulator of the TGF-β family signaling pathway by interacting with its downstream transcription factors, R-Smads. We found that Man1 protein was phosphorylated and altered subcellular localization upon activin treatment. Furthermore, activin treatment resulted in reduction of man1 gene expression. Our data suggest that Man1 is itself regulated by TGF-β/activin, and provide new insights into the regulatory mechanisms of TGF-β signaling pathway.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、TGF-βシグナル伝達を負に制御するMAN1自身が、TGF-β/アクチビンによって制御を受けることを示しており、多様なTGF-βシグナル伝達様式の一端の解明に繋がると考えられ、学術的意義が高い。また、TGF-β/アクチビンによる核膜蛋白質の輸送制御や核のリモデリングが予想され、核膜の性質変化がもたらす細胞外シグナル応答や組織分化への影響について、次の展開が期待される。