Study of PICT1-mediated nucleolar stress response and tumorigenesis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kobe University
• Principal Investigator: Maehama Tomohiko 神戸大学, 医学研究科, 准教授 (40322755)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 核小体ストレス / PICT1

Outline of Final Research Achievements

The nucleolus is a site for ribosome biogenesis and surveillance center for this process. Impaired ribosome biogenesis, which is detected in the nucleolus, induces nucleolar stress response, eventually leading to p53 activation, followed by cell cycle arrest and/or apoptotic cell death. In this study, we found that (1) a particular region of pre-rRNA regulates the binding of nucleolar protein PICT1 and its stabilizer X; (2) nucleolar stress decreased the amount of pre-rRNA to induce dissociation of PICT1-X complex; (3) the dissociated PICT1 became unstable and degraded then triggered the signal that led to p53 activation.

Free Research Field

生化学・分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、これまでほとんど解明されていなかった核小体ストレス応答の分子機構、特にストレスを検知する分子の同定に大きく近づいたと思われる。核小体ストレスはp53を活性化して細胞増殖の停止や細胞死誘導を引き起こす内在性の経路として近年注目されており、本研究によって同定された分子群を標的とした創薬、中でも抗がん薬の開発への応用が期待できる。