Nrf2 activation mechanism mediated by amino acid starvation response factor GCN1L1

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659122
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Hirosaki University
• Principal Investigator: ITOH Ken 弘前大学, 医学(系)研究科(研究院), 教授 (10323289)
• Co-Investigator(Renkei-kenkyūsha): MIMURA Junsei 弘前大学, 医学(系)研究科(研究院), 講師 (60344884)
• Project Period (FY): 2012-04-01 – 2013-03-31
• Keywords: アミノ酸飢餓 / GCN2 / GCN1 / 酸化ストレス

Research Abstract

Nrf2 plays an important role in oxidative stress response in animals. On the other hand, yeast GCN1 plays an essential role in amino acid starvation response. In this study, we found that GCN1L1, a human homologue of GCN1, directly binds to
Nrf2 and that GCN1L1 knockdown diminishes Nrf2 response in various human cancer cells and mouse fibroblasts. Furthermore, Nrf2 was activated by the amino acid starvation. These results suggest the cross talk of Nrf2 stress response with amino acid starvation response pathway.

Research Products

• [Journal Article] Nrf2 activation is associated with Z-DNA formation in the human HO-1 promoter (2013)
  • Author(s): Maruyama A, Mimura J, Harada N, Itoh K
  • Journal Title: Nucleic Acids Res Volume: 41 Pages: 5223-5234
  • DOI: 10.1093/nar/gkt243
  • Peer Reviewed
• [Journal Article] Carnosic acid suppresses the production of amyloid-β 1-42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells (2013)
  • Author(s): Meng P, Yoshida H, Matsumiya T, Imaizumi T, Tanji K, Xing F, Hayakari R, Dempoya J, Tatsuta T, Aizawa-Yashiro T,Mimura J, Kosaka K, Itoh K, Satoh K
  • Journal Title: Neurosci Res Volume: 75 Pages: 4-102
  • DOI: 10.1016/j.neures.2012.11.007
  • Peer Reviewed
• [Journal Article] Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases (2013)
  • Author(s): Tanji K, Maruyama A, Odagiri S, Mori F, Itoh K, Kakita A, Takahashi H, Wakabayashi K
  • Journal Title: J Neuropathol Exp Neurol Volume: 72 Pages: 18-28
  • DOI: 10.1097/NEN.0b013e31827b5713
  • Peer Reviewed
• [Journal Article] Nrf2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation (2012)
  • Author(s): Harada N, Ito K, Hosoya T, Mimura J, Maruyama A, Noguchi N, Yagami KI, Morito N, Takahashi S, Maher JM, Yamamoto M, Itoh K
  • Journal Title: Free Radic Biol Med Volume: 53 Pages: 2256-2262
  • DOI: 10.1016/j.freeradbiomed.2012.10.001
  • Peer Reviewed
• [Journal Article] Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis (2012)
  • Author(s): Okada K, Warabi E, Sugimoto H, Horie M, Tokushige K, Ueda T, Harada N, Taguchi K, Hashimoto E, Itoh K, Ishii T, Utsunomiya H, Yamamoto M, Shoda J
  • Journal Title: J Gastroenterol Volume: 47 Pages: 924-935
  • DOI: 10.1007/s00535-012-0552-9
  • Peer Reviewed
• [Presentation] The role of ribosomal interacting protein GCN1L1 in oxidative stress-mediated Nrf2 activation (2014)
  • Author(s): Liu T, Kimura S, Yamazaki H, Maruyama A, Nishikawa K, Harada N, Mimura J, Yamamoto M, Itoh K
  • Organizer: 17th Bennial Meeting of Society for Free Radical Research International
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 20140323-26
• [Presentation] Nrf2転写調節経路とeIF2aリン酸化経路とのクロストーク (2013)
  • Author(s): 伊東健
  • Organizer: 日本放射線影響学会第56回大会
  • Place of Presentation: ホテルクラウンパレス,青森
  • Year and Date: 20131018-20
• [Presentation] 酸化ストレスで活性化する転写経路のクロストーク (2013)
  • Author(s): 伊東健
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌,札幌
  • Year and Date: 20130606-08
• [Presentation] アミノ酸飢餓応答因子GCN1L1によるNrf2活性制御機構の解析 (2012)
  • Author(s): 伊東健、 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 福岡国際会議場 (福岡)
  • Year and Date: 20121214-16
• [Presentation] The role of ribosome interac ti-ng protein GCN1L1 in oxidative stre ss-mediated Nrf2 activation (2012)
  • Author(s): Ken Itoh
  • Organizer: Internati onal symposium 2012 on Signaling, Func tion of Reactive Oxygen Species
  • Place of Presentation: Kyushu University Station -I for Collaboration Research (Fukuoka)
  • Year and Date: 2012-12-17
• [Remarks]
  • URL: http://www.med.hirosaki-u.ac.jp/~admed/department/index.html