Regulation of neural stem cell proliferation and differentiation switching by SBNO1

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22735
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Ihara Dai 滋賀医科大学, 医学部, 助教 (40884367)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: Sbno1 / Otub1 / p53 / 神経幹細胞

Outline of Final Research Achievements

In this study, we focused on switching function of self-renewal for neuron production in neural stem cells. We focused on SBNO1 as a molecule that regulates these neural stem cell functions. p53 is ectopically upregulated in the cerebrum of Sbno1 ko mice. Previous studies have shown that p53 deficiency in neural stem cells causes cortical hypertrophy, suggesting that p53 regulates the number of differentiated neurons. We have identified the p53 deubiquitinating enzyme OTUB1 as a partner molecule of SBNO1. In steady state cells, p53 is degraded by ubiquitination quickly after expression. However, when OTUB1 is expressed, ubiquitination of p53 is immediately removed and the p53 protein is spared from degradation. We confirmed this binding by immunoprecipitation. We also analyzed the expression of both proteins in neural stem cells and found that both proteins localized to the nucleus. Through this study, we have elucidated part of the mechanism by which SBNO1 regulates p53 via OTUB1.

Free Research Field

神経発生

Academic Significance and Societal Importance of the Research Achievements

本研究ではp53の新規制御機構の解明を通して、神経幹細胞がどの様に自己複製とニューロン産生を制御しているのか解析した。正常な神経幹細胞の分裂の破綻は精神疾患の病因となる。精神疾患の診断は客観的な指標が乏しいことから、細胞・分子レベルでの各疾患の病態メカニズムを解明することが求められている。Sbno1は様々な精神疾患に寄与する可能性が報告されている。これらの報告からSBNO1がヒトの脳の正常な発達と機能に重要であることは示唆されるがどのように精神疾患の発症に関わっているかは明らかになっていない。本研究は将来的に、精神疾患の客観的な診断方法や治療戦略のための新しい指標を示すことができるであろう。