N-terminal hydrophobic amino acids of ATF5 protein confer IL-1b-induced stabilization, and responsible for the suppression of the serum amyloid A1 (SAA1) ans SAA2 gene expression

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TAKAHASHI shigeru 東京薬科大学, 生命科学部, 准教授 (10266900)
• Project Period (FY): 2011 – 2013
• Keywords: ATF5 / ストレス / 急性期応答 / 炎症

Research Abstract

In this study, we show that IL-1b, a proinflammatory cytokine, increases the expression of ATF5 protein in HepG2 cells in part by stabilizing the ATF5 protein. The N-terminal domain rich in hydrophobic amino acids that is predicted to form a hydrophobic network was responsible for destabilization in steady-state conditions and served as an IL-1b response domain. Furthermore, IL-1b increased the translational efficiency of ATF5 mRNA via the 5' UTR a and phosphorylation of the eukaryotic translation initiation factor 2a (eIF2a). ATF5 knockdown in HepG2 cells up-regulated the IL-1b-induced expression of the serum amyloid A1 (SAA1) and SAA2 genes. Our results show that the N-terminal hydrophobic amino acids play an important role in the regulation of ATF5 protein expression in IL-1b-mediated immune response and that ATF5 is a negative regulator for IL-1b-induced expression of SAA1 and SAA2 in HepG2 cells.

Research Products

• [Journal Article] N-terminal Hydrophobic Amino Acids of Activating Transcription Factor 5 (ATF5) Protein Confer Interleukin 1β(IL-1β)-induced Stabilization (2014)
  • Author(s): Abe T., Kojima M., Akanuma S., Iwashita H., Yamazaki T., Okuyama R., Ichikawa K., Umemura M., Nakano H., Takahashi S., Takahashi Y.
  • Journal Title: J . Biol. Chem Volume: 289 Pages: 3888-3900
• [Journal Article] The 5'-untranslated region regulates ATF5 mRNA stability via nonsense-mediated mRNA decay in response to environmental stress (2013)
  • Author(s): Hatano M., Umemura M., Kimura N., Yamazaki T., Takeda H., Nakano H., Takahashi S., Takahashi Y.
  • Journal Title: F EBS J Volume: 280 Pages: 4693-4707
• [Journal Article] Phenolic diterpenes from rosemary suppress cAMP responsiveness of gluconeogenic gene promoters (2013)
  • Author(s): Yun Y.S., Noda S., Shigemori G., Kuriyama R., Takahashi S., Umemura M., Takahashi Y., Inoue H.
  • Journal Title: Phytother Res Volume: 27 Pages: 906-910
• [Presentation] マウス鋤鼻細胞の増殖とアポトーシスに関与する転写因子ATF5 (2014)
  • Author(s): 鈴木誠人, 飯田吉剛, 青木満里恵, 笹川洋, 中野春男, 梅村真理子, 高橋滋, 高橋勇二
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 東京
  • Year and Date: 20140300
• [Presentation] 転写因子ATF5による嗅覚受容体の発現調節 (2014)
  • Author(s): 金子将人, 雨宮ゆう子, 中野春男, 梅村真理子, 高橋滋, 高橋勇二
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 東京
  • Year and Date: 20140300
• [Presentation] マウス鋤鼻器における転写因子ATF5の機能解析 (2013)
  • Author(s): 飯田吉剛, 鈴木誠人, 青木満里恵, 笹川洋, 中野春男, 梅村真理子, 高橋滋, 高橋勇二
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20131200
• [Presentation] 炎症性サイトカインIL-1βによるATF5タンパク質安定化とその役割 (2013)
  • Author(s): 阿部貴則, 岩下弘実, 奥山隆一, 山崎高志, 高橋滋, 高橋勇二
  • Organizer: 東京薬科大学医薬工3大学包括連携推進シンポジウム
  • Place of Presentation: 八王子
  • Year and Date: 20131200
• [Presentation] ATF5欠損マウスの脳内モノアミン量の解析 (2013)
  • Author(s): 森直人, 梅村真理子,松崎彩子,中野春男,高橋滋,高橋勇二
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 20130900
• [Presentation] IL-1βによるATF5タンパク質安定化の免疫応答における役割 (2013)
  • Author(s): 阿部貴則, 岩下弘実, 奥山隆一, 山崎高志, 高橋滋, 高橋勇二
  • Organizer: 日本生化学会関東支部例会
  • Place of Presentation: 甲府
  • Year and Date: 20130600
• [Presentation] 環境ストレスによるC/EBPγmRNAの安定化制御 (2012)
  • Author(s): 大川佳子, 山﨑高志, 中野春男, 梅村真理子, 高橋滋, 高橋勇二
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 博多
  • Year and Date: 20121200
• [Presentation] ATF5/C/EBPγheterodimer regulates sodium-arsenite induced DR5 gene expression in human hepatoma cells (2012)
  • Author(s): 山﨑高志, 阿部貴則, 中野春男, 梅村真理子, 高橋滋, 高橋勇二
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 博多
  • Year and Date: 20121200
• [Presentation] ATF5 mRNA 5'非翻訳領域を介したNMDによる新規ストレス応答性mRNA安定化機構 (2012)
  • Author(s): 幡野仁哉, 梅村真理子, 中野春男, 高橋滋, 高橋勇二
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都
  • Year and Date: 20120300
• [Presentation] The 5'-untranslated region regulates the stability of ATF5mRNA by nonsense-mediated mRNA decay (2011)
  • Author(s): Umemura, M., Hatano, M., Kimura, N., Yamazaki, T., Takeda, H., Nakano, H., Takahashi, S., Takahashi, Y.
  • Organizer: Cold spring harbor laboratory the 2011 meeting on eukaryotic mRNA processing
  • Place of Presentation: New York, USA(国内学会発表)
  • Year and Date: 20110800