Molecular basis of physiological and pathological regulation by endoplasmic reticulum stress response

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H01424
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: Imaizumi Kazunori 広島大学, 医系科学研究科(医), 教授 (90332767)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 細胞・組織 / シグナル伝達 / 細胞生物学 / 小胞体ストレス / ストレスセンサー

Outline of Final Research Achievements

We focused on the metabolism, activation, and intracellular function of BBF2H7 and OASIS, that are endoplasmic reticulum stress sensors, and analyzed the details of the physiological roles they have. 1) We found that small peptide derived from BBF2H7 is produced in response to ER stress, and the peptide is easy to aggregate, suggesting that the proteolysis of BBF2H7 dependent on ER stress may be involved in the pathogenesis of neurodegenerative diseases. 2) p21 was identified as a transcription target of OASIS, which was proven to be a cellular senescence-promoting factor. We succeeded in developing a new cancer treatment strategy to stop the cell growth of cancer cells by epigenome editing of oasis gene that was methylated at its promoter region. 3) The mucopolysaccharide-causing molecule IDS is degraded by ERAD pathway. Folding of mutant IDS was promoted through activation of calnexin cycle by blocking the ERAD pathway and the activities of mutant IDS was found to be recovered.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

小胞体ストレス応答機構が小胞体以外のオルガネラ機能に大きな影響を与えていることを分子実体として証明した学術的意義は大きい。また、それらの機能制御が神経変性疾患、癌、希少難病の治療につながる可能性を見出したことは社会的にも意義深い。