Disruption of transcription network of cellular genes by human T-cell leukemia virus type-1.

• Project/Area Number: 22501000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: Tokushima Bunri University
• Principal Investigator: OHSHIMA Takayuki 徳島文理大学, 香川薬学部, 准教授 (10397557)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ウイルス / HTLV-1 / 転写制御 / HBZ / 発がん / オートファジー / 細胞死 / 薬学 / 遺伝子 / 応用微生物 / SUMO化修飾 / 翻訳後修飾

Research Abstract

Human T-cell leukemia virus type-1 (HTLV-1) infection causes adult T-cell leukemia (ATL). Modulation of the transcriptional control of cellular genes by HTLV-1 is thought to be associated with the development of ATL. The viral protein HTLV-1 basic leucine-zipper factor (HBZ) has been shown to dysregulate the activity of cellular transcription factors. We evidence that HBZ reduced both IRF-1 DNA-binding activity and stability via a proteasome-dependent pathway. In addition, IRF-1-mediated apoptosis is significantly reduced by ectopic production of the HBZ. Also, we demonstrate that HBZ is exported from the nucleus to the cytoplasm, where it activates the mTOR signaling pathway through an association with growth arrest and DNA damage gene 34 (GADD34). Starvation-induced autophagy is significantly suppressed by the overexpression of HBZ.

Research Products

• [Journal Article] Protein inhibitor of activated STAT, PIASy regulates alpha-smooth muscle actin expression by interacting with E12 inmesangial cells. (2012)
  • Author(s): Kazuo Torikoshi, Hideharu Abe, Takeshi Matsubara, Takahiro Hirano, Takayuki Ohshima, Taichi Murakami, Makoto Araki, Akira Mima, Noriyuki Iehara, Atsushi Fukatsu, Toru Kita, Hideyuki Arai, and Toshio Doi.
  • Journal Title: PLoS One Volume: 7
• [Journal Article] Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1. (2011)
  • Author(s): Risa Mukai, and Takayuki Ohshima.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 409 Pages: 328-332
• [Journal Article] Dual effects of HTLV-1 bZIP factor in suppression of interferon regulatory factor 1 (2011)
  • Author(s): Risa Mukai, Takayuki Ohshima
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 409 Pages: 328-332
  • Peer Reviewed
• [Journal Article] HTLV-1 basic leucine-zipper factor, HBZ, interacts with MafB and suppreses transcription through a Maf recognision element. (2010)
  • Author(s): Takayuki Ohshima, Risa Mukai, Norie Nakahara, Jun Matsumoto, Osamu Isono, Yusuke Kobayashi, Satoru Takahashi, and Kunitada Shimotohno.
  • Journal Title: J. Cell. Biochem. Volume: 111 Pages: 187-194
• [Journal Article] Transcriptional repression by sumoylation of Epstein-Barr virus BZLF1 protein correlates with association of histone deacetylase. (2010)
  • Author(s): Takayuki Murata, Naoe Hotta, Shigenori Toyama, Sanae Nakayama, Shigeru Chiba, Hiroki Isomura, Takayuki Ohshima, Teru Kanda, and Tatsuya Tsurumi.
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 23925-23935
• [Journal Article] HTLV-1 basic leucine-zipper factor, HBZ, interacts with MafB and suppresses transcription through a Maf recognition element. (2010)
  • Author(s): Takayuki Ohshima, 他7名
  • Journal Title: J.Cell.Biochem. Volume: 111 Pages: 187-194
  • Peer Reviewed
• [Journal Article] Transcriptional repression by sumoylation of Epstein-Barr virus BZLFl protein correlates with association of histone deacethylase. (2010)
  • Author(s): Takayuki Murata, 他9名
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 23925-23935
  • Peer Reviewed
• [Journal Article] HTLV-1 HBZ positively regulates the mTOR signaling pathway via inhibition of GADD34 activity in the cytoplasm.
  • Author(s): Risa Mukai, and Takayuki Ohshima.
  • Journal Title: Oncogene Volume: (in press)
• [Presentation] HTLV-1 HBZ activates mTOR signaling pathway via inhibition of GADD34 (2011)
  • Author(s): Risa Mukai, and Takayuki Ohshima.
  • Organizer: 15th International Conference on Human Retrovirology: HTLV and Related viruses
  • Place of Presentation: Belgium
• [Presentation] Ubiquitination-mediated degradation and DNA-binding impairment of IRF-1 were induced by HTLV-1 HBZ (2011)
  • Author(s): Risa Mukai, and Takayuki Ohshima.
  • Organizer: International Union of Microbiological Societies 2011Congress
  • Place of Presentation: Sapporo
• [Presentation] HTLV-1 HBZ activates mTOR signaling pathway via inhibition of GADD34 (2011)
  • Author(s): Risa Mukai, Takayuki Ohshima
  • Organizer: 15^<th> International Conference on Human Retrovirology : HTLV and Related viruses
  • Place of Presentation: Belgium
• [Presentation] mTORシグナルの活性化におけるHTLV-1 HBZタンパク質の役割 (2010)
  • Author(s): 向井理紗、大島隆幸
  • Organizer: BMB2010
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] HTLV-1HBZは転写因子largeMafファミリーと相互作用してMafの活性を抑制する (2010)
  • Author(s): 向井理紗、大島隆幸
  • Organizer: 第9回次世代を担う若手ファーマ・バイオフォーラム2010
  • Place of Presentation: 京都
• [Presentation] HTLV-1HBZタンパク質によるmTORシグナルの活性制御機構 (2010)
  • Author(s): 向井理紗、大島隆幸
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
• [Presentation] mTORシグナルの活性化におけるHTLV-1HBZタンパク質の役割 (2010)
  • Author(s): 向井理紗、大島隆幸
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://kp.bunri-u.ac.jp/course/yakuji_k.html