Regulatory mechanism of expression of ETS transcription factor Myeloid elf-1-like factor (MEF) by tumor suppressors

• Project/Area Number: 23590082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: SUICO Mary Ann Soten 熊本大学, 大学院生命科学研究部(薬), 助教 (20363525)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 転写因子 / がん抑制遺伝子 / MEF / 低酸素 / HIF1 / ETS転写因子 / 癌抑制遺伝子 / 翻訳後発現調節 / p53 / MDM2 / Rb / 翻訳後発現制御

Research Abstract

Myeloid elf-1-like factor (MEF) functions as transcriptional factor and plays critical roles in development, cellular differentiation, proliferation, transformation and immune responses. In the present study, we aim to determine the regulatory mechanisms of MEF expression by several cellular factors. First, we demonstrated that tumor suppressor p53 decreases the level of MEF protein through the induction of transcription of MDM2, an E3 ubiquitin ligase. Moreover, the findings also revealed that another tumor suppressor Rb increases the MEF protein level possibly by stabilizing its protein expression. Finally, our data further showed that hypoxia increases both the mRNA and protein levels of MEF through HIF1alpha, the main effector molecule of hypoxia. On the whole, the findings revealed in these studies provide a better understanding of how the transcriptional regulator MEF is influenced by tumor suppressors such as p53 and Rb, and by hypoxia-related protein HIF1alpha.

Research Products

• [Journal Article] Mild electrical stimulation at 0.1-ms pulse width induces p53 protein phosphorylation and G2 arrest in human epithelial cells. (2013)
  • Author(s): Fukuda ft, Suico MA, Koyama K, Omachi K, Kai Y, Matsuyama S, Mitsutake K, Taura M, Mo rino-Koga S, Shuto T, Kai H.
  • Journal Title: Journal of Biological Chemistry Volume: 288(22) Issue: 22 Pages: 16117-16126
  • DOI: 10.1074/jbc.m112.442442
  • Peer Reviewed
• [Journal Article] Rb/E2F1 regulates the innate immune receptor Toll-like receptor 3 in epithelial cells (2012)
  • Author(s): Taura M., et.al.
  • Journal Title: Molecular and Cellular Biology Volume: 32(8) Issue: 8 Pages: 1581-1590
  • DOI: 10.1128/mcb.06454-11
  • Peer Reviewed
• [Journal Article] STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. (2012)
  • Author(s): Sato T., et.al.
  • Journal Title: Molecular Cell Volume: 47(1) Issue: 1 Pages: 99-110
  • DOI: 10.1016/j.molcel.2012.04.015
  • Peer Reviewed
• [Journal Article] Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome. (2012)
  • Author(s): Tomoaki Koga
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: 43852-43852
  • DOI: 10.1371/journal.pone.0043852
  • Peer Reviewed
• [Journal Article] Diethyldithiocarbamate induces apoptosis in HHV-8-infected primary effusion lymphoma cells via inhibition of the NF-κB pathway. (2012)
  • Author(s): Matsuno T, Kariya R, Yano S, Morino-Koga S, Taura M, Suico MA, Shimauchi Y, Matsuyama S, Okamoto Y, Shuto T, Kai H, Okada S.
  • Journal Title: Int J Oncol. Volume: 40(4) Pages: 1071-1078
  • Peer Reviewed
• [Journal Article] Synergism Between Interleukin (IL)-17 and Toll-like Receptor 2 and 4 Signals to Induce IL-8 Expression in Cystic Fibrosis Airway Epithelial Cells. (2012)
  • Author(s): Mizunoe S, Shuto T, Suzuki S, Matsumoto C, Watanabe K, Ueno-Shuto K, Suico MA, Onuki K, Gruenert DC, Kai H.
  • Journal Title: J Pharmacol Sci. Volume: -
  • Peer Reviewed
• [Journal Article] Hyperthermia With Mild Electrical Stimulation Protects Pancreatic β-Cells From Cell Stresses and Apoptosis. (2012)
  • Author(s): Kondo T, Sasaki K, Matsuyama R, Morino-Koga S, Adachi H, Suico MA, Kawashima J, Motoshima H, Furukawa N, Kai H, Araki E.
  • Journal Title: Diabetes. Volume: 61(4) Pages: 838-847
  • Peer Reviewed
• [Journal Article] Rb/E2F1 Regulates the Innate Immune Receptor Toll-Like Receptor 3 in Epithelial Cells. (2012)
  • Author(s): Taura M, Suico MA, Koyama K, Komatsu K, Miyakita R, Matsumoto C, Kudo E, Kariya R, Goto H, Kitajima S, Takahashi C, Shuto T, Nakao M, Okada S, Kai H.
  • Journal Title: Mol Cell Biol. Volume: 32(8) Pages: 1581-1590
  • Peer Reviewed
• [Journal Article] MEF/ELF4 transactivation by E2F1 is inhibited by p53 (2011)
  • Author(s): Taura M, Suico MA, Fukuda R, Koga T, Shuto T, Sato T, Morino-Koga S, Okada S, Kai H
  • Journal Title: Nucleic Acids Res Volume: 39 Issue: 1 Pages: 76-88
  • DOI: 10.1093/nar/gkq762
  • Peer Reviewed
• [Journal Article] Glucose Uptake in Rat Skeletal Muscle L6 Cells Is Increased by Low-Intensity Electrical Current Through the Activation of the Phosphatidylinositol-3-OH kinase (PI-3K) / Akt Pathway. (2011)
  • Author(s): Yano S, Morino-Koga S, Kondo T, Suico MA, Koga T, Shimauchi Y, Matsuyama S, Shuto T, Sato T, Araki E, Kai H.
  • Journal Title: J Pharmacol Sci. Volume: 115(1) Pages: 94-98
  • Peer Reviewed
• [Presentation] Functional interplay of p53 and TLR links immune response and cancer (2014)
  • Author(s): Mary Ann SUICO
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] Specific pulse-width mild electrical stimulation induces p53 activation via p38 MAPK and ameliorates LPS-induced inflammatory cytokine response (2013)
  • Author(s): K. Omachi
  • Organizer: 15th International congress of immunology
  • Place of Presentation: Milano, ITALY
• [Presentation] p53 regulates the Ets trascription factor MEF/Elf4 via MDM2 (2013)
  • Author(s): スイコ メリーアン
  • Organizer: 第２回次世代創薬研究者養成塾
  • Place of Presentation: 熊本大学薬学部（熊本市中央区）
• [Presentation] Specific pulse-width mild electrical stimulation induces p53 activation via p38 MAPK and ameliorates LPS-induced inflammatory cytokine response (2013)
  • Author(s): R. Fukuda, K. Omachi, M. A. Suico, K. Koyama, Y. Kai, S. Matsuyama, K. Mitsutake, S. Morino-Koga, T. Shuto, H. Kai
  • Organizer: 15th International congress of immunology
  • Place of Presentation: Mico Milano Congressi, Milano, ITALY
• [Presentation] Crucial role of basal p53 in attenuation of inflammation and fibrosis in hereditary glomerular nephritis, Alport syndrome (2013)
  • Author(s): R. Fukuda, K. Koyama, T. Koga, Y. Kai, K. Omachi, K. Motomura, M. A. Suico, T. Shuto, H. Kai
  • Organizer: 15th International congress of immunology
  • Place of Presentation: Mico Milano Congressi, Milano, ITALY
• [Presentation] 慢性腎疾患 Alport syndrome モデルマウスを用いた癌抑制遺伝子p53の腎保護的機能の解明 (2013)
  • Author(s): 福田 亮介
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] p53 regulates the Ets transcription factor MEF/Elf4 via MDM2 (2012)
  • Author(s): Mary Ann SUICO
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道
• [Presentation] p53 regulates the Ets transcription factor MEF/Elf4 via MDM2 (2012)
  • Author(s): Mary Ann SUICO
  • Organizer: ASCB 2012 Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] 慢性腎疾患Alport syndromeモデルマウスを用いた癌抑制遺伝子p53の腎保護的機能の解明 (2012)
  • Author(s): 福田 亮介
  • Organizer: 第65回日本薬理学会西南部会
  • Place of Presentation: 熊本大学（熊本県）
• [Presentation] p53 regulates the Ets transcription factor MEF/Elf4 via MDM (2012)
  • Author(s): Mary Ann Suico
  • Organizer: 第71回日本癌学会学術総会-がん研究とライフサイエンスの更なるリエゾン-
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] 慢性腎疾患Alport syndromeにおける癌抑制遺伝子p53の腎保護的機能の解明 (2012)
  • Author(s): 福田 亮介
  • Organizer: 第11回次世代を担う若手ファーマ・バイオフォーラム
  • Place of Presentation: 九州大学（福岡県）
• [Presentation] Specified pulse-width mild electrical stimulation induces p53 phosphorylation and transcriptional activation (2012)
  • Author(s): Ryosuke Fukuda
  • Organizer: ＩＣＨＯ＆ＪＣＴＭ 2012
  • Place of Presentation: ハイアットリージェンシー京都（京都府）
• [Presentation] p53 regulates the Ets transcription factor MEF/Elf4 via MDM2 (2012)
  • Author(s): M. Suico
  • Organizer: ASCB 2012 Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Mef/Elf4 transactivation by E2F1 is inhibited by p53 (2011)
  • Author(s): Mary Ann SUICO
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] The tumor suppressor Retinoblastoma protein positively regulates innate immune receptor Toll-like receptor 3 in epithelial cells (2011)
  • Author(s): K. Koyama
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
• [Presentation] Protective effects of p53 in a mouse model of progressive hereditary kidney disease Alport syndrome (2011)
  • Author(s): R. Fukuda
  • Organizer: ASCB 51st Annual Meeting
  • Place of Presentation: Denver, USA
• [Presentation] Mef/Elf4 transactivation by E2F1 is inhibited by p53. (2011)
  • Author(s): M. Suico, M. Taura, R. Fukuda, T. Koga, T. Shuto, T. Sato, S. Morino, S. Okada, H. Kai
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（京都）
• [Presentation] ストレス耐性付与および脂肪蓄積抑制作用を有する新たなphysical medicine (2011)
  • Author(s): 松山 真吾、矢野 脩一郎、古賀（森野） 佐緒里、島内 裕一郎、岡本 友加、四反田 伊穂李、メリーアン スイコ、首藤 剛、甲斐 広文
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡大学薬学部（福岡）
• [Presentation] 遺伝性腎疾患Alport症候群における癌抑制遺伝子p53の腎病態進行抑制機構の解明 (2011)
  • Author(s): 福田 亮介 、小山 皓介、古賀 友紹、甲斐 友佳理、メリーアン スイコ、首藤 剛、甲斐 広文
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡大学薬学部（福岡）
• [Presentation] 翻訳後N型糖鎖修飾によるトランスサイレチンの新規小胞体品質管理機構 (2011)
  • Author(s): 庄 美里、佐藤 卓史、迫 康弘、桃原 真美子、西頭 英起、金子 雅幸、メリーアン スイコ、首藤 剛、甲斐 広文
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡大学薬学部（福岡）
• [Presentation] 糖尿病性腎症に対する新たなphysical medicineの病態改善効果 (2011)
  • Author(s): 岡本 有加、古賀（森野） 沙緒里 、古賀 友紹 、大町 紘平、メリーアン スイコ、首藤 剛、甲斐 広文
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡大学薬学部（福岡）
• [Presentation] 遺伝性腎疾患alport症候群に対する新たなphysical medicineの腎病態改善効果 (2011)
  • Author(s): 甲斐 友佳理、古賀 友紹 、福田 亮介、古賀（森野） 沙緒里 、メリーアン スイコ、小山 皓介、佐藤 卓史、首藤 剛、甲斐 広文
  • Organizer: 第28回日本薬学会九州支部大会
  • Place of Presentation: 福岡大学薬学部（福岡）
• [Presentation] Mild electrical stimulation suppresses fat accumulation and increases stress resistance via mitochondrial membrane potentioal-dependent activation of AMP-activated protein kinase. (2011)
  • Author(s): Shingo Matsuyama, Shuichiro Yano, Saori Koga-Morino, Yuichiro Shimauchi, Yuka Okamoto, Ihori Shitanda, Mary Ann Suico, Tsuyoshi Shuto, Hirofumi Kai
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] The tumor suppressor Retinoblastoma protein positively regulates innate immune receptor Toll-like receptor 3 in epithelial cells. (2011)
  • Author(s): Kosue Koyama, Manabu Taura, Mary Ann Suico, Tsuyoshi Shuto, Seiji Okada, Hirofumi Kai
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] HRD1-dependent endoplasmic reticulum-associated degradation pathway is involved in the clearance of transthyretin variant. (2011)
  • Author(s): Misato Sho, Takashi Sato, Yasuhiro Sako, Mamiko Momohara, Hideki Nishitoh, Masayuki Kaneko, Mary Ann Suico, Tsuyoshi Shuto and Hirofumi Kai
  • Organizer: 5th International Congress on Stress Response in Biology and Medicine
  • Place of Presentation: Loews Hotel Le Concorde,Quebec(Canada)
• [Presentation] Protective effects of p53 in a mouse model of progressive hereditary kidney disease Alport syndrome. (2011)
  • Author(s): R. Fukuda, K. Koyama, T. Koga, Y. Kai, M. A. Suico, T. Shuto, H. Kai
  • Organizer: ASCB 51st Annual Meeting
  • Place of Presentation: Colorado Convention Center,Denver(USA)
• [Remarks]
  • URL: http://www.molmed730.org/
• [Remarks] 熊本大学薬学部遺伝子機能応用学研究室
  • URL: http://molmed730.org/index.html
• [Remarks] 熊本大学大学院薬学教育部 遺伝子機能応用学研究室
  • URL: http://molmed730.org/index.html
• [Remarks]
  • URL: http://molmed730.org/