Analysis on relationship between nuclear envelope homeostasis and accumulation of ER-resident transmembrane transcription factor OASIS at nuclear bleb

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16076
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Matsuhisa Koji 広島大学, 医系科学研究科(医), 助教 (60735299)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 核膜ストレス / OASIS

Outline of Final Research Achievements

Genomic DNA is protected by nuclear membrane. It is known that various stresses including DNA damage, induce injury of nuclear membrane. The nuclear membrane damage facilitate DNA damage and cause oncogenic transformation. We found that endoplasmic reticulum-resident transcription factor OASIS accumulate at the damage sites of nuclear membrane. The accumulation is triggered by disruption of nuclear lamina. N-terminal cytoplasmic region of OASIS is important for the accumulation. Furthermore, we observed that OASIS interacts with inner nuclear membrane protein LAP2beta, which plays important roles in nuclear envelope repair. These results suggest the possibility that OASIS plays pivotal roles in the repair of nuclear envelope.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

近年、核膜の構造異常は早老症や癌の発症・病態形成に関与していると言われている。本研究課題においてOASISが核膜の異常構造へと集積して核膜の保護あるいは修復に重要な役割を果たすことが示唆された。このことは、上記疾患の病態形成メカニズムを理解するための重要な知見となる。またそのメカニズムを基に核膜保護や損傷修復を亢進させることが出来れば、上記疾患の予防法あるいは治療法の開発へと繋がることが期待される。