Development of ER quality monitoring probe to characterize the oral tissue disease

• Project/Area Number: 25670790
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: University of Miyazaki
• Principal Investigator: NISHITOH Hideki 宮崎大学, 医学部, 教授 (00332627)
• Co-Investigator(Renkei-kenkyūsha): KADOWAKI Hisae 宮崎大学, 医学部, 助教 (40568200)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ストレス / 可視化 / ストレス応答

Outline of Final Research Achievements

When the functional quality of the endoplasmic reticulum (ER) is reduced, unfolded proteins accumulate in the ER. We tried to express the fluorescent protein GFP in the ER lumen and monitor the amount of unfolded proteins. As technical hurdle to do that, GFP in the ER is lower fluorescence intensity because of the loose of three-dimensional structure with the disulfide bond. To solve this problem, GFP variants having no cysteine [GFPCys (-)] was carried out. By using this probe, this gene was introduced into various cells and we succeeded in visualizing the ER stress conditions in living cells.

Research Products

• [Journal Article] GCN5 is essential for IRF-4 gene expression followed by transcriptional activation of Blimp-1 in immature B cells. (2014)
  • Author(s): Kikuchi H, Nakayama M, Kuribayashi F, Imajoh-Ohmi S, Nishitoh H, Takami Y, Nakayama T.
  • Journal Title: J Leukoc Biol Volume: 95 Issue: 3 Pages: 399-404
  • DOI: 10.1189/jlb.0413232
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The expression of Fn14 via mechanical stress-activated JNK contributes to apoptosis induction in osteoblasts. (2014)
  • Author(s): Matsui, H., Fukuno, N., Kanda, Y., Kantoh, Y., Chida, T., Nagaura, Y., Suzuki, O., Nishitoh, H., Takeda, K., Ichijo, H., Sawada, Y., Sasaki, K., Kobayashi, T. and Tamura, S.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 10 Pages: 6438-6450
  • DOI: 10.1074/jbc.m113.536300
  • Peer Reviewed / Open Access
• [Journal Article] Protein kinase Cθ gene expression is oppositely regulated by GCN5 and EBF1 in immature B cells. (2014)
  • Author(s): Kikuchi H, Nakayama M, Kuribayashi F, Imajoh-Ohmi S, Nishitoh H, Takami Y, Nakayama T
  • Journal Title: FEBS Lett Volume: 588 Issue: 9 Pages: 1739-1742
  • DOI: 10.1016/j.febslet.2014.03.025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells. (2014)
  • Author(s): Kikuchi H., Nakayama M., Kuribayashi F., Imajoh-Ohmi S., Nishitoh H., Takami Y., Nakayama T.
  • Journal Title: Gene Volume: 544 Issue: 1 Pages: 19-24
  • DOI: 10.1016/j.gene.2014.04.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] "Derlin Family Proteins Control Protein Loading into the Endoplasmic Reticulum via Substrate-Specific Cotranslational Rerouting from Translocation to Degradation" (2014)
  • Author(s): Hisae Kadowaki, Hideki Nishitoh
  • Organizer: EMBOカンファレンス
  • Place of Presentation: バルセロナ
  • Year and Date: 2014-10-26 – 2014-10-31
• [Presentation] 小胞体ストレス誘導性翻訳時分解の分子機構の解明 (2014)
  • Author(s): 門脇寿枝、西頭英起
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15
• [Presentation] 小胞体品質管理におけるDerlinの生理的意義の解析 (2014)
  • Author(s): 西頭英起
  • Organizer: 第9回小胞体ストレス研究会
  • Place of Presentation: 徳島
  • Year and Date: 2014-07-04 – 2014-07-05
• [Presentation] The molecular mechanism of novel ER quality control system (2014)
  • Author(s): Kadowaki, H., Nishitoh, H.
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-11 – 2014-06-13
• [Presentation] Derlinファミリーを介した小胞体品質管理システム (2014)
  • Author(s): 門脇寿枝, 西頭英起
  • Organizer: 平成26年度日本生化学会九州支部例会
  • Place of Presentation: 博多
  • Year and Date: 2014-05-17 – 2014-05-18
• [Presentation] Derlinファミリーを介した小胞体品質管理システム (2013)
  • Author(s): 西頭英起
  • Organizer: 第86回日本生化年会シンポジウム
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 小胞体ストレス誘導性翻訳時分解の分子機構の解明 (2013)
  • Author(s): 門脇寿枝 一條秀憲 西頭英起
  • Organizer: 第86回日本生化年会
  • Place of Presentation: 横浜
• [Presentation] Tuning of IRE1α-Mediated Protein Degradation by the Atg5-Atg12 Conjugate (2013)
  • Author(s): 加藤裕紀 西頭英起 北村正敬
  • Organizer: 第86回日本生化年会
  • Place of Presentation: 横浜
• [Presentation] GCN5 is essential for IRF-4 gene expression followed by transcriptional activation of Blimp-1 in immature B cells (2013)
  • Author(s): Kikuchi, H. Nakayama, M. Kuribayashi, F. Imajoh-Ohmi, S. Nishitoh, H. Takami, Y. Nakayama, T.
  • Organizer: 第86回日本生化年会
  • Place of Presentation: 横浜
• [Presentation] GCN5 protects vertebrate cells against UV-irradiation via controlling gene expression of DNA polymerase η (2013)
  • Author(s): Kikuchi, H. Kuribayashi, F. Imajoh-Ohmi, S. Nishitoh, H. Takami, Y. Nakayama, T.
  • Organizer: 第7回日本エピジェネティクス研究会年会
  • Place of Presentation: 奈良
• [Presentation] 小胞体の品質管理システムとその破綻による疾患
  • Author(s): 西頭英起
  • Organizer: 埼玉医科大学卒後教育委員会後援学術集会
  • Place of Presentation: 埼玉医科大学
  • Invited