The impact of fatty aldehyde metabolism in Fanconi anemia

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06487
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Kobe University
• Principal Investigator: Sakai Wataru 神戸大学, バイオシグナル総合研究センター, 助教 (70526251)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ファンコニ貧血 / アルデヒド代謝

Outline of Final Research Achievements

In this project, an interaction factor with FANCD2 protein was identified from mass spectrum-based proteome screening. Genetic analysis with knockout cell lines of the FANCD2 interacting factor revealed the impact of endogenous fatty aldehyde molecules on genome stability. In situ proximity ligation assay revealed co-localization of FANCD2 and the interacting factor in not only the nucleus but also cytoplasm. Moreover, live cell imaging of EGFP-FANCD2 expressing cell line recognized a novel intracellular dynamics of FANCD2 in response to formation of organelles that are important for the regulation of lipid metabolism. This intracellular dynamics of FANCD2 have not been reported previously, and this is a novel cellular response of FANCD2 upon the lipid metabolism. These results indicate a possible function of FANCD2 independent of the DNA damage response.

Free Research Field

分子生物学、細胞生物学、化学物質影響

Academic Significance and Societal Importance of the Research Achievements

稀な遺伝疾患であるファンコニ貧血は多種多様な病態を示すことが知られている。それらは責任遺伝子産物FAタンパク質の機能異常に起因するが、脂質代謝異常に関してはその病態発症機序は依然として明らかでなく、根本的な治療法や予防法の開発も進んでいない。本研究課題ではFAタンパク質のひとつであるFANCD2と協調して機能する因子の同定およびその解析から、FANCD2の脂質代謝制御における新たな細胞応答を明らかにした。これらの研究成果は、ファンコニ貧血の病態発症機序の解明、および分子メカニズムに基づいた病態緩和法の開発の基盤になると期待される。