Studies on selective translation mechanism of stress response Protein under global translational repression

• Project/Area Number: 22700892
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Tumor biology
• Research Institution: 公益財団法人がん研究会 (2011); Japanese Foundation For Cancer Research (2010)
• Principal Investigator: TSUKUMO Yosinori 公益財団法人がん研究会, がん化学療法センターゲノム研究部, 研究員 (40469630)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 翻訳 / ストレス応答タンパク / 小胞体 / mRNA / リボソーム / 翻訳開始因子 / 腫瘍 / 飢餓

Research Abstract

Upon endoplasmic reticulum(ER) stress, PKR-like ER-resident kinase(PERK) phosphorylates eukaryotic translation initiation factor 2 alpha(eIF2α), resulting in reducing global translation while promoting translation reinitiation of upstream open reading frame(uORF)-containing mRNAs, such as ATF4.We showed transducin(beta)-like 2(TBL2) as a novel ER-anchored adaptor protein that promotes the PERK-mediated translation reinitiation for cell survival.

Research Products

• [Journal Article] Hyperactivation of 4E-binding protein 1 as a mediator of iguanide-induced cytotoxicity during glucose deprivation. (2012)
  • Author(s): Matsuo J, Tsukumo Y, Saito S, Tsukahara S, Sakurai J, Sato S, Kondo H, Ushijima M, Matsuura M, Watanabe T, Tomida A
  • Journal Title: Mol. Cancer Ther. Volume: 11(5) Pages: 1082-1091
  • DOI: 10.1158/1535-7163.mct-11-0871
  • Peer Reviewed
• [Journal Article] Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced cytotoxicity during glucose deprivation (2012)
  • Author(s): Junichi Matsuo, Yoshinori Tsukumo (co-first), et al
  • Journal Title: Molecular Cancer Therapeutics Volume: 11 Pages: 1082-91
  • Peer Reviewed
• [Presentation] ビグアナイド系化合物による4E-BP1の活性化と抗腫瘍効果 (2011)
  • Author(s): 築茂由則、近藤裕道、冨田章弘
  • Organizer: 分指標的治療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-23
• [Presentation] Hyper-activation of 4E-binding protein 1 by anti-diabetic biguanide as its anti-tumor mechanisms of action (2011)
  • Author(s): Yoshinori Tsukumo, Junichi Matsuo, Satomi Tsukahara, Junko Sakurai, Toshiki Watanabe, Sigeo Sato, Hiromichi Kondo, and Akihiro Tomida
  • Organizer: American Association for Cancer Research, Special conference
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2011-02-26
• [Presentation] Hyper-activation of 4E-binding protein 1 by anti-diabetic biguanide as its anti-tumor mechanisms of action (2011)
  • Author(s): 築茂由則
  • Organizer: American Association for Cancer Research, Special conference, "Targeting PI3K/mTOR signaling in cancer"
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2011-02-26
• [Presentation] ビグアナイド系化合物による4E-BP1の活性化と抗腫瘍効果 (2011)
  • Author(s): 築茂由則
  • Organizer: 分子標的治療学会
  • Place of Presentation: 東京ホテル日航東京
• [Remarks]
  • URL: http://www.jfcr.or.jp/chemotherapy/department/genome/index.html