Analysis of HTLV-1 Tax-induced IKK activation pathway

• Project/Area Number: 26840062
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: The University of Tokyo
• Principal Investigator: SHIBATA Yuri 東京大学, 医科学研究所, 助教 (20722573)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: HTLV-1 Tax / ATL / ユビキチン修飾 / NF-kappaB / NF-κB

Outline of Final Research Achievements

HTLV-1 Tax-induced persistent activation of transcription factor NF-κB is crucial for cell immortalization and the onset of ATL. Here, we analyzed the precise mechanism underlying Tax-induced NF-κB activation pathway. We found that Tax induces hybrid ubiquitin chains, which enhance the formation of macromolecular complex of active IKK complex.

Research Products

• [Journal Article] Structures of CYLD USP with Met1- or Lys63-linked diubiquitin reveal mechanisms for dual specificity (2015)
  • Author(s): Sato, Y., Goto, E., Shibata, Y., Kubota, Y., Yamagata, A., Goto-Ito, S., Kubota, K., Inoue, J., Takekawa, M., Tokunaga, F. and Fukai, S.
  • Journal Title: Nat. Struct. Mol. Biol. Volume: 22 Issue: 3 Pages: 222-229
  • DOI: 10.1038/nsmb.2970
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Analysis of HTLV-1 Tax-induced IKK activation pathway (2016)
  • Author(s): Yuri Shibata、Jun-Ichiro Inoue
  • Organizer: Keystone Symposia Conference NF-kappaB and MAP Kinase Signaling in Inflammation
  • Place of Presentation: Whistler (Canada)
  • Year and Date: 2016-03-13
  • Int'l Joint Research
• [Presentation] HTLV-1 Tax誘導性のIKK複合体活性化におけるポリユビキチン鎖の機能解析 (2015)
  • Author(s): 柴田 佑里、井上純一郎
  • Organizer: 第二回日本HTLV-1学会学術集会
  • Place of Presentation: 東京大学医科学研究所 (東京都 港区)
  • Year and Date: 2015-08-22
• [Presentation] Identification of ubiquitin ligase involved in the HTLV-1 Tax-induced IKK activation (2014)
  • Author(s): Yuri Shibata, Jun-ichiro Inoue
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Identification of ubiquitin ligase involved in the HTLV-1 Tax-induced IKK activation (2014)
  • Author(s): Yuri Shibata, Jun-ichiro Inoue
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 (神奈川県横浜市)
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] HTLV-1 TaxによるIKK複合体活性化に必要な因子の同定と解析 (2014)
  • Author(s): 柴田 佑里、尾山 大明、秦 裕子、井上 純一郎
  • Organizer: 第1回日本HTLV-1学会学術集会
  • Place of Presentation: 東京大学医科学研究所 (東京都港区)
  • Year and Date: 2014-08-23 – 2014-08-24
• [Remarks] 東京大学医科学研究所分子発癌分野ホームページ
  • URL: http://www.traf6.com