NMD mediated new stress response mechanism

• Project/Area Number: 19590232
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TAKAHASHI Sigeru Tokyo University of Pharmacy and Life Science, 生命科学部, 准教授 (10266900)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 遺伝子 / 栄養学 / 環境 / ストレス / 遺伝子発現 / 転写因子 / ATF5 / 環境応答 / 発現制御

Research Abstract

ATF5 mRNAは通常状態ではuORFからの翻訳によるATF5翻訳領域内でのストップコドンの発生によりNMDによる分解を受けている。一方、ストレス環境下では本来の翻訳開始点からの翻訳が起る事によるNMDシステムからの回避が起り、mRNAの安定性が増加する。その結果、ATF5の発現量が上昇し、標的遺伝子の発現が引き起こされ、ATF5を介したストレス応答が形成されることがわかった。

Research Products

• [Journal Article] NMR metabolic profiling on highly-diluted neonatal mouse urine (2009)
  • Author(s): Shimizu, Y, I, Sunaga, E., Aoyagi, S., Kanazawa, K., Aul Takahashi, S.AulnoneAstrikeO , Takahashi, Y., and Nemoto, T.
  • Journal Title: J. Toxicol. Sci b0 (In Press)
• [Journal Article] Fasting induced up-regulation of activating transcription factor 5 in mouse liver Life Sci (2009)
  • Author(s): Shimizu, Y, I, Morita, M., Ohmi, A., Aoyagi, S., Ebihara, H., Tonaki, D., Horino, Y., Iijima, M., Hirose, H., Aul Takahashi, S. AulnoneAstrike0 and Takahashi, Y.
  • Journal Title: b0(In Press)
• [Journal Article] Cadmium interferes with the degradation of ATF5 via a post-ubiquitination step of the proteasome degradation pathway Biochemical and Biophysical Research Communications (2009)
  • Author(s): Uekusa H., Namimatsu M., Hiwatashi Y., Akimoto T., Nishida T., Aul Takahashi S AulnoneAstrikeO . Takahashi Y
  • Journal Title: b0380(3) Pages: 673-678
• [Journal Article] Cadmium interferes with the degradation of ATF5 via a ppost-ubiquitination step of the proteasome degradation pathway (2009)
  • Author(s): Uekusa, et al.
  • Journal Title: Biochemical and Biophysical Research Communication 380 Pages: 673-678
  • Peer Reviewed
• [Journal Article] Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated region (2008)
  • Author(s): Watatani, Y., Ichikawa, K., Nakanishi, N., Fujimoto, M., Takeda, H., Kimura, N., Hirose, H., Aul Takahashi, S.AulnoneAstrikeO, Takahashi, Y.
  • Journal Title: J. Biol. Chem. b0, 283 Pages: 2543-2553
• [Journal Article] Stress-induced Translation of ATF5 mRNA Is Regulated by the 5'-Untranslated Region (2008)
  • Author(s): Watatani, et. al.
  • Journal Title: J. Biol. Chem. 283 Pages: 2543-2553
  • Peer Reviewed
• [Journal Article] Aminoacid limitation induces expression of ATF5mRNA at post-transcriptional levels (2007)
  • Author(s): Watatani, Y., Kimura, N., Tonaki, D., Hirose, H., Aul Takahashi, S.AulnoneAstrikeO, Takahashi, Y.
  • Journal Title: Life Sciences b0, 80 Pages: 879-885
• [Presentation] 5'-untranslated region modulates the stability of ATF5 mRNA in response to oxidative stress (2008)
  • Author(s): Shigeru Takahashi, Hitoshi Takeda, Mariko Umemura, Natsumi Kimura, Katsunori Utsuki, Yujiro Watatani, Noriko Nakanishi, Kenji Ichikawa, Ryuichi Okuyama, Yuji Takahashi
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学大会合同大会
  • Place of Presentation: 神戸シンポジウム、「ストレス応答と転写因子」
  • Year and Date: 2008-12-12
• [Presentation] 5'-untranslated region modulates the stability of ATF5 mRNA in response to cellular stress (2008)
  • Author(s): Takahashi, et al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会 シンポジウム
  • Place of Presentation: 神戸市神戸ポートアイランド
  • Year and Date: 2008-12-12
• [Presentation] ストレス応答性転写因子ATF5によるAARE配列を介したCHOP遺伝子の転写活性化 (2008)
  • Author(s): 山崎高志、大味麻子、加藤研司、車谷春香、山本宙享、高橋滋、高橋勇二
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 新生仔マウス尿を対象とした微量試料へのNMR-メタボリック・プロファイリング法の応用の試み (2008)
  • Author(s): 清水悠介、須永絵里、青柳俊、中村明日香、広瀬秀徳、高橋滋、根本直、高橋勇二
  • Organizer: 第62回日本栄養・食糧学会大会
  • Place of Presentation: 埼玉
  • Year and Date: 2008-05-02
• [Presentation] 絶食ストレスによるATF5 とその近位逆行遺伝子の誘導的発現 (2007)
  • Author(s): 清水悠介、青柳俊、森田桃子、中村明日香、広瀬秀徳、高橋滋、高橋勇二
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 転写因子ATF5mRNAの5'UTRは、ストレスに応答して、NMDによるmRNAの不安定化機構を調節する (2007)
  • Author(s): 竹田仁、木村なつみ、宇津木克紀、綿谷裕二郎、市川研史、広瀬秀徳、高橋滋、高橋勇二
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Upstream open reading frame modulates the NMD-mediated destabilization of ATF5 mRNA in response to cellular stress (2007)
  • Author(s): Takeda,H., Kimura, N., Watatani, Y., Utsugi, K., Ichikawa, K., Uekusa, H., Nakanishi, N., Hirose, H., Takahashi, S., Takahashi, Y.
  • Organizer: Cold Spring Harbor Laboratory the 2007 meeting on Eukaryotic mRNA Processing.(b0)
  • Place of Presentation: New York, USA
  • Year and Date: 2007-08-24
• [Presentation] Upstream open reading frame modulates the NMD-mediated destabilization of ATF5 mRNA in response to cellular stress (2007)
  • Author(s): Takeda, et. al.
  • Organizer: Cold Spring Harbor Laboratory the 2007 meeting on Eukaryotic mRNA Processing.
  • Place of Presentation: New York, USA
  • Year and Date: 2007-08-24
• [Presentation] Expression of activating transcription factor 5 (ATF5) in cryptic region of mouse intestinal epithelium (2007)
  • Author(s): Aoyagi, S., Morita, M., Nakamura, A., Shimizu, Y.I. Hirose, H., Takahashi, S., Takahashi, Y.
  • Organizer: FASEB Meeting b0 : Gastrointestinal Tract XII : The Molecular & Integrative Basis for GI Development, Homeostasis & Diseas
  • Place of Presentation: Colorado, USA
  • Year and Date: 2007-08-11