Mechanism of growth inhibition by overexpression explored from the expression level of the limiting mutant protein

• Project/Area Number: 20H03242
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: Okayama University
• Principal Investigator: Moriya Hisao 岡山大学, 環境生命自然科学学域, 教授 (60500808)
• Co-Investigator(Kenkyū-buntansha): 牧野 能士 東北大学, 生命科学研究科, 教授 (20443442)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2023: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 酵母 / 過剰発現 / タンパク質 / 細胞毒性 / タンパク質毒性 / プロテオスタシス / システムバイオロジー / 量感受性遺伝子 / 増殖阻害

Outline of Research at the Start

タンパク質の過剰発現は細胞機能に様々な悪影響を及ぼすが、そのメカニズムはほとんど分かっていない。本研究では、出芽酵母をモデル生物として、わずかに過剰発現しただけで増殖阻害を起こす「量感受性タンパク質」を対象とし、それらがどのようなメカニズムで増殖阻害を起こすのかを調査する。特に本研究では、これらのタンパク質の機能欠失変異体を体系的調査することで、過剰発現による増殖阻害のメカニズムを体系化する。

Outline of Final Research Achievements

Overexpression of proteins can harm cells in various ways. Using budding yeast as a model for eukaryotic cells, we have investigated the characteristics of protein groups that cause growth inhibition when overexpressed and have classified the mechanisms of growth inhibition. In this study, we further explored the toxicity mechanisms by introducing mutations into proteins that cause growth inhibition. As a result, we revealed that the presence of specific amino acids or the activity of the protein itself can lead to growth inhibition.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまでほとんど分かっていないタンパク質の発現を制約するメカニズムの解明につながり、基礎生物学的な知識の拡張に繋がる。また、ここで得られた知識は、細胞にタンパク質が蓄積することにより生じる疾患、癌や神経変性疾患などの細胞の生理状態の理解と創薬へと繋がるとともに、細胞工学において特定のタンパク質を大量発現させたいときのタンパク質デザインの指針となる。

Research Products

• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] トロント大学(カナダ)
• [Journal Article] Protein sorting upon exit from the endoplasmic reticulum dominates Golgi biogenesis in budding yeast (2024)
  • Author(s): Sasaki Saku、Schlarmann Philipp、Hanaoka Kazuki、Nishii Hinako、Moriya Hisao、Mu?iz Manuel、Funato Kouichi
  • Journal Title: FEBS Letters Volume: 598 Issue: 5 Pages: 548-555
  • DOI: 10.1002/1873-3468.14830
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments (2023)
  • Author(s): Saeki Nozomu、Yamamoto Chie、Eguchi Yuichi、Sekito Takayuki、Shigenobu Shuji、Yoshimura Mami、Yashiroda Yoko、Boone Charles、Moriya Hisao
  • Journal Title: PLOS Genetics Volume: 19 Issue: 4 Pages: e1010732-e1010732
  • DOI: 10.1371/journal.pgen.1010732
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Demonstration of iodide-dependent UVA-triggered growth inhibition in Saccharomyces cerevisiae cells and identification of its suppressive molecules (2023)
  • Author(s): Ono Ryota、Saeki Nozomu、Kojima Keiichi、Moriya Hisao、Sudo Yuki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 677 Pages: 1-5
  • DOI: 10.1016/j.bbrc.2023.07.048
  • Peer Reviewed
• [Journal Article] Massive expression of cysteine-containing proteins causes abnormal elongation of yeast cells by perturbing the proteasome (2022)
  • Author(s): Namba Shotaro、Kato Hisaaki、Shigenobu Shuji、Makino Takashi、Moriya Hisao
  • Journal Title: G3 Genes|Genomes|Genetics Volume: - Issue: 6
  • DOI: 10.1093/g3journal/jkac106
  • Peer Reviewed / Open Access
• [Journal Article] Identification of uncharacterized proteins potentially localized to mitochondria (UPMs) in <scp> <i>Saccharomyces cerevisiae</i> </scp> using a fluorescent protein unstable in the cytoplasm (2021)
  • Author(s): Horiuchi Satoshi、Namba Shotaro、Saeki Nozomu、Satoh Ayano、Moriya Hisao
  • Journal Title: Yeast Volume: 39 Issue: 5 Pages: 303-311
  • DOI: 10.1002/yea.3685
  • Peer Reviewed
• [Remarks] 岡山大学細胞システム化学研究室
  • URL: https://tenure5.vbl.okayama-u.ac.jp/HMlab/
• [Remarks] 酵母とシステムバイオロジーブログ
  • URL: https://tenure5.vbl.okayama-u.ac.jp/HM_blog/
• [Remarks] 岡山大学 細胞システム化学 守屋研究室
  • URL: https://tenure5.vbl.okayama-u.ac.jp/HMlab/
• [Remarks] 酵母とシステムバイオロジー
  • URL: https://tenure5.vbl.okayama-u.ac.jp/HM_blog/
• [Remarks] 岡山大学システム細胞学研究室
  • URL: https://tenure5.vbl.okayama-u.ac.jp/HMlab/
• [Remarks] 酵母とシステムバイオロジー（ブログ）
  • URL: https://tenure5.vbl.okayama-u.ac.jp/HM_blog/