Activation of NF-kB2 in adult T-cell leukemia

• Project/Area Number: 19591099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Niigata University
• Principal Investigator: FUJII Masahiro Niigata University, 医歯学系, 教授 (30183099)
• 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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: HTLV-1 / ATL / NF-Kb / CD4 / NF-kB / NF-kB2 / WNK1 / Rel / 遺伝子変異 / 染色体転座

Research Abstract

成人T細胞白血病(ATL)は極めて悪性の白血病であり、有効な抗がん剤も開発されていない.ATLの発症に転写因子NF-kBの異常活性化が関与することが知られているが、その分子機構は不明である.ATL細胞から染色体転座に伴う活性化型NF-kB2遺伝子(NF-kB2/p58)を単離した.正常なNF-kB2とは異なり、NF-kB2/p58は恒常的に遺伝子発現を誘導することが示された.以上の結果は、NF-kB2の遺伝子異常が一部のATL発症に関与する可能性を示している.

Research Products

• [Journal Article] Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-{kappa} B (2009)
  • Author(s): Zhao T, Yasunaga JI, Satou Y, Nakao M, Takahashi M, Fujii M, Matsuoka M
  • Journal Title: Blood 113(12) Pages: 2755-2764
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia virus type 1 Tax induces an aberrant clustering of the tumor suppressor Scribble through the PDZ domain binding motif dependent and independent interaction (2008)
  • Author(s): Okajima M, Takahashi M, Masaya Higuchi, Ohsawa T, Yoshida S, Yoshida Y, Oie M, Tanaka T, Gejyo F, Fujii M
  • Journal Title: Virus Genes 37(2) Pages: 231-240
  • Peer Reviewed
• [Journal Article] Knockdown of synapse-associated protein D1g1 reduces syncytium formation induced by human T-cell leukemia virus type 1 (2008)
  • Author(s): Yoshida S, Higuchi M, Shoji T, Yoshita M, Ishioko K, Takahashi M, Oie M, Tanaka Y, Uchiyama M, Fujii M
  • Journal Title: Virus Genes 37(1) Pages: 9-15
  • Peer Reviewed
• [Journal Article] Rearranged NF-kappa B2 gene in an adult T-cell leukemia cell line (2008)
  • Author(s): Isogawa M, Higuchi M, Takahashi M, Oie M, Mori N, Tanaka Y, Aoyagi Y, Fujii M
  • Journal Title: Cancer Science 99(4) Pages: 792-798
  • Peer Reviewed
• [Journal Article] Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia (2008)
  • Author(s): Nakayawa T, Hieshima K, Arao T, Jin Z, Nagakubo D, Shirakawa AK, Yamada Y, Fujii M, Oiso N, Kawada A, Nishio K, Yoshie O
  • Journal Title: Oncogene 27(23) Pages: 3221-3232
  • Peer Reviewed
• [Journal Article] Rearranged NF-kB2 gene in an adult T-cell leukemia cell line (2008)
  • Author(s): Isogawa M
  • Journal Title: Cancer Science 99(4) Pages: 792-798
  • Peer Reviewed
• [Journal Article] Rearranged NF-kB2 gene in an adult T-cell leukemia cell line (2008)
  • Author(s): Isogawa M
  • Journal Title: Cancer Science (In press)
  • Peer Reviewed
• [Journal Article] Cooperation of NF-kB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV) Taxl but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T cell line (2007)
  • Author(s): Higuchi M, Tsubata C, Kondo R, Yoshida S, Takahashi M, Oie M, Tanaka Y, Mahieux R, Matsuoka M, Fujii M
  • Journal Title: J Virol. 81(21) Pages: 11900-11907
  • Peer Reviewed
• [Journal Article] Cooperation of NF-kB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type 1 (HTLV) Taxl but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T cell line (2007)
  • Author(s): Higuchi M
  • Journal Title: J Virol. 81 Pages: 11900-11907
  • Peer Reviewed
• [Journal Article] Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia (2007)
  • Author(s): Nakayama T
  • Journal Title: Oncogene (In press)
  • Peer Reviewed
• [Journal Article] Isolation and characterization of a novel human parechovirus from various clinical samples (2007)
  • Author(s): Watanabe K
  • Journal Title: Emerg. Inf. Dis. 13 Pages: 889-895
  • Peer Reviewed
• [Journal Article] A novel KRAB-Zinc finger protein interacts with latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus and activates transcription viaterminal repeat sequences (2007)
  • Author(s): Watanabe A
  • Journal Title: Virus Genes 34 Pages: 127-136
  • Peer Reviewed
• [Presentation] Identification of a critical region of HTLV-1 Taxl for NF-kB2/p100 activation (2008)
  • Author(s): 樋口雅也
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Activation of PI3k/Akt substitues a function of PDZ domain binding motif of HTLV-1 Tax in its T-cell transformation (2008)
  • Author(s): 藤井雅寛
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] HTLV-1Taxl と HTLV-2Tax2によるIL-2非依存性細胞増殖誘導能の違い (2008)
  • Author(s): 藤井雅寛
  • Organizer: 第56回日本ウイルス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2008-10-26
• [Presentation] HTLV-1 感染伝播へのPDZドメイン蛋白D1g1の関与 (2007)
  • Author(s): 樋口雅也
  • Organizer: 第55回日本ウイルス会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-22
• [Presentation] HILV-1感染伝播へのPDZドメイン蛋白Dlg1の関与 (2007)
  • Author(s): 樋口雅也
  • Organizer: 第55回日本ウイルス会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-22
• [Presentation] 新型ヒトパレコウイルス6型の性状解析と新潟県におけるヒトパレコウイルスの分離状況 (2007)
  • Author(s): 渡邉香奈子
  • Organizer: 第55回日本ウイルス会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-22
• [Presentation] Distinct T-cell transformation mechanisms of HTLV-1 Taxl and HTLV-2 Taxl2 (2007)
  • Author(s): 藤井雅寛
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] HTLV-1 b ZIP factor suppresses canonical pathway of NF-kB by physical interaction with the p65 (2007)
  • Author(s): Tiejun Zhao
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Isolation of a rearranged NF-kB2 gene from an adult T cell leukemia cell line (2007)
  • Author(s): 樋口雅也
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Heterodimer formation of Fra-2 and JunD promotes CCR4 expression and proliferation in adult T-cell leukemia (2007)
  • Author(s): Takashi Nakayama
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Distinct T-cell transformation mechanisms of HTLV-1 Tax1 and HTLV-2 Tax2 (2007)
  • Author(s): 藤井雅寛
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Activation of NF-kB2/p100 by human T-cell leukemia virus type 1 (HTLV-1) Taxl but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T-cell line (2007)
  • Author(s): Masaya Higuchi
  • Organizer: 13^<th> international conference of human retrovirology HTLV and related viruses
  • Place of Presentation: 箱根
  • Year and Date: 2007-05-22
• [Presentation] Activation of NF-kB2/p100 by human T-cell leukemia virus type 1(HTLV-1)Taxl but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T-cell line (2007)
  • Author(s): Masaya Higuchi
  • Organizer: 13th international conference of human retrovirology HTLV and related viruses
  • Place of Presentation: 箱根
  • Year and Date: 2007-05-22
• [Book] ヒトT細胞白血病ウイルス (2007)
  • Author(s): 藤井雅寛
  • Publisher: 医薬ジャーナル社
• [Book] HTLV-1と疾患 (2007)
  • Author(s): 藤井雅寛
  • Publisher: 文光堂
• [Book] ヒトT細胞白血病ウイルス(HTLV-1の分子生物学) (2007)
  • Author(s): 藤井雅寛
  • Publisher: 医薬ジャーナル社
• [Book] HTLV-1と疾患(HTLV-2) (2007)
  • Author(s): 藤井雅寛
  • Publisher: 文光堂