The pathogenic mechanism of HTLV-1 leukemogenesis via novel binding protein of Tax1

• Project/Area Number: 23790498
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Niigata University
• Principal Investigator: TAKAHASHI Masahiko 新潟大学, 医歯学系, 助教 (80377192)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: HTLV-1 / Tax1 / USP10 / ストレス顆粒 / 活性酸素種 / ROS / G3BP1

Research Abstract

We examined functional roles of USP10 and its binding partner G3BP1. We found that G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10. However, following exposure to arsenic, G3BP1 and USP10 induce the formation of stress granules, which uncovers the antioxidant activity of USP10. We also found that the antioxidant activity of USP10 requires the protein kinase activity of ATM.

Research Products

• [Journal Article] Stress granules inhibit apoptosis by reducing reactive oxygen species production. (2013)
  • Author(s): Masahiko Takahashi
  • Journal Title: Molecular and Cellular Biology Volume: 33 Issue: 4 Pages: 815-829
  • DOI: 10.1128/mcb.00763-12
  • Peer Reviewed
• [Journal Article] Both G3BP1 and G3BP2 contribute to stress granule formation. (2013)
  • Author(s): Hideaki Matsuki
  • Journal Title: Genes to Cells Volume: 18 Issue: 2 Pages: 135-146
  • DOI: 10.1111/gtc.12023
  • Peer Reviewed
• [Journal Article] Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize human CD4+ T cells. (2013)
  • Author(s): Michitaka Imai
  • Journal Title: Virus Genes Volume: 46 Issue: 1 Pages: 39-46
  • DOI: 10.1007/s11262-012-0831-9
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia virus type 1 Tax protein interacts with and mislocalizes the PDZ domain protein MAGI-1 (2013)
  • Author(s): Grace Naswa Makokha
  • Journal Title: Cancer Science Volume: 104 Issue: 3 Pages: 313-320
  • DOI: 10.1111/cas.12087
  • Peer Reviewed
• [Journal Article] Activation of mTOR by human T-cell leukemia virus type 1 Tax is important for the transformation of mouse T cells to interleukin-2-independent growth (2011)
  • Author(s): Manami Yoshita
  • Journal Title: Cancer Science Volume: 103巻 Issue: 2 Pages: 369-374
  • DOI: 10.1111/j.1349-7006.2011.02123.x
  • Peer Reviewed
• [Presentation] Stress granules inhibit apoptosis by reducing ROS production, and this is nullified by HTLV-1 Tax1 (2012)
  • Author(s): 高橋雅彦
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] USP10は亜ヒ酸によるHTLV-1感染細胞のアポトーシス感受性に関与する (2012)
  • Author(s): 高橋雅彦
  • Organizer: 第5回HTLV研究会およびシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-08-25
• [Presentation] ストレス顆粒はROS産生を抑制することによりアポトーシスを阻害するが、これをHTLV-1のTax1は解除する
  • Author(s): 高橋 雅彦
  • Organizer: 日本癌学会
  • Place of Presentation: ロイトン札幌（北海道）