Viral oncogenesis and NF-kappaB

• Project/Area Number: 17013029
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YAMAOKA Syoji Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 教授 (90263160)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥47,000,000 (Direct Cost: ¥47,000,000); Fiscal Year 2009: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2008: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2007: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2006: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2005: ¥9,400,000 (Direct Cost: ¥9,400,000)
• Keywords: HTLV-I / NF-kappaB / 乳癌 / 大腸癌 / 肺癌 / NIK / 成人T細胞白血病 / スタチン / ゲラニル化 / ホジキン病 / 癌 / ウイルス / インターフェロン / IKK / 阻害剤 / ATL / Hodgkin

Research Abstract

This research has aimed at understanding the mechanism of carcinogenesis and identifying molecular targets for therapy through elucidating molecular mechanisms of constitutive NF-kappaB activation in virus-infected cells. I reported that NF-kappaB inducing kinase (NIK) is over-expressed and constitutively activated at the pre-translational level in adult T-cell leukemia cells as well as in lung cancer cells, and thus could be an attractive molecular target for therapy.

Research Products

• [Journal Article] Overexpression of NF-kappaB inducing kinase underlies constitutive NF-kappaB activation in lung cancer cells (2010)
  • Author(s): Saitoh Y, 他
  • Journal Title: Lung Cancer (in press)
  • Peer Reviewed
• [Journal Article] CADM1 interacts with Tiam1 and promotes invasive phenotype of human T-cell leukemia virus type I-transformed cells and adult T-cell leukemia cells (2010)
  • Author(s): Suzuki S, 他
  • Journal Title: J Biol Chem. 14;285(20) Pages: 1511-1522
  • Peer Reviewed
• [Journal Article] Human T cell lymphotropic virus 1 manipulates interferon regulatory signals by controlling the TAK1-IRF3 and IRF4 pathways (2010)
  • Author(s): Suzuki S, 他
  • Journal Title: J Biol Chem. 12;285(7) Pages: 4441-4446
  • Peer Reviewed
• [Journal Article] Role for protein geranylgeranylation in adult T-cell leukemia cell survival. (2009)
  • Author(s): Nonaka M, Uota S, Saitoh Y, Takahashi M, Sugimoto H, Amet T, Arai A, Miura O, Yamamoto N, *Yamaoka S
  • Journal Title: Exp Cell Res 315 Pages: 141-50
• [Journal Article] Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation (2009)
  • Author(s): 徳永、山岡、他
  • Journal Title: Nat Cell Biol 11 Pages: 123-132
  • Peer Reviewed
• [Journal Article] Inhibition of IkappaB kinase beta restrains oncogenic proliferation of pancreatic cancer cells. (2008)
  • Author(s): Ochiai T, Saito Y, Saitoh T, Dewan MZ, Shioya A, Kobayashi M, Kawachi H, Muto S, Itai A, Uota S, Eishi Y, Yamamoto N, Tanaka S, Arii S, *Yamaoka S.
  • Journal Title: J Med Dent Sci. 55 Pages: 49-59
• [Journal Article] Overexpressed NF-kappaB-inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells. (2008)
  • Author(s): Saitoh, Y., N. Yamamoto, M.Z. Dewan, H. Sugimoto, V.J. Martinez Bruyn, Y. Iwasaki, K. Matsubara, X. Qi, T. Saitoh, I. Imoto, J. Inazawa, A. Utsunomiya, T. Watanabe, T. Masuda, *Yamaoka S.
  • Journal Title: Blood 111 Pages: 5118-5129
• [Journal Article] Role for protein geranylgeranylation in adult T-cell leukemia cell survival (2008)
  • Author(s): 野中、山本(直)、山岡、他
  • Journal Title: Exp Cell Res 315 Pages: 141-150
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia virus type 1 Tax modulates interferon-alpha signal transduction through competitive usage of the coactivator CBP/p300 (2008)
  • Author(s): Zhang, 山岡、下遠野、他
  • Journal Title: Virology 379 Pages: 306-13
  • Peer Reviewed
• [Journal Article] Pycnogenol, a procyanidin-rich extract from French maritime pine, inhibits intracellular replication of HIV-1 as well as its binding to host cells (2008)
  • Author(s): Feng, 山本(直)、山岡、吉仲、他
  • Journal Title: Jpn J Infect Dis 61 Pages: 279-285
  • Peer Reviewed
• [Journal Article] A single amino acid substitution in the S1 and S2 Spikep rotein domains determines the neutralization escape phenotype of SARS-CoV (2008)
  • Author(s): 光木、山本(直)、山岡、横田, 他
  • Journal Title: Microbes Infect 10 Pages: 908-915
  • Peer Reviewed
• [Journal Article] Spread of a large plasmid carrying the cpe gene and the tcp locus amongst Clostridium perfringens isolales from nosocomial outbreaks and sporadic cases of gastroenteritis in a geriatric hospital (2008)
  • Author(s): 小林、山本(直)、山岡、稲松、他
  • Journal Title: Epidemiol Infect 137 Pages: 108-113
  • Peer Reviewed
• [Journal Article] Statin-induced inhibition of HIV-1 release from latently infected U1 cells reveals a critical role for protein prenylation in HIV-1 replication (2008)
  • Author(s): Amet、山本(直)、山岡、他
  • Journal Title: Microbes Infect 10 Pages: 471-480
  • Peer Reviewed
• [Journal Article] Overexpressed NF-kappaB-inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells (2008)
  • Author(s): 斎藤、山本(直)、山岡、他
  • Journal Title: Blood 111 Pages: 5118-5129
  • Peer Reviewed
• [Journal Article] Overexpressed NF-κB inducingkinase contributes to tumorigenesis of a du1t T-cell leukemia and Hodgkin Reed-Sternberg cells (2008)
  • Author(s): 斎藤、山岡ほか
  • Journal Title: Blood (印刷中)
  • Peer Reviewed
• [Journal Article] Inhibition of IκB kinaseβ restrains oncogenic proliferation of pancreatic (2008)
  • Author(s): 落合、山岡ほか
  • Journal Title: Jornal of Medical and Dental Sciences (印刷中)
  • Peer Reviewed
• [Journal Article] Up-regulation of hepatitis C virus replication by human T cell leukemia virus type I-encoded Tax protein. (2007)
  • Author(s): Zhang、山岡、下遠野ほか
  • Journal Title: Virology 369 Pages: 198-205
  • Peer Reviewed
• [Journal Article] Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti. (2007)
  • Author(s): Sebban-Benin H, Yamaoka S, Courtois G. ほか
  • Journal Title: Hum Mol Genet. 16 Pages: 2805-2815
  • Peer Reviewed
• [Journal Article] Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappaB. (2007)
  • Author(s): 鈴木、櫻井、山岡ほか
  • Journal Title: J Biol Chem 282 Pages: 25177-81
  • Peer Reviewed
• [Journal Article] Efficient induction of HIV-I replication in latently infected cells through contact with CD4(+) T cells : Involvement of NF-kappaB activation (2007)
  • Author(s): Xiaohua Qiほか
  • Journal Title: Virology (印刷中)
• [Journal Article] Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages (2007)
  • Author(s): Takayoshi Suganamiほか
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology 27 Pages: 84-91
• [Journal Article] Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1. (2006)
  • Author(s): Saitoh T, Tun-Kyi A, Ryo A, Yamamoto M, Finn G, Fujita T, Akira S, Yamamoto N, Lu KP, *Yamaoka S.
  • Journal Title: Nat Immunol. 7 Pages: 598-605
• [Journal Article] A20. (2006)
  • Author(s): Saitoh, H., *Yamaoka S
  • Journal Title: AfCS-Nature Molecule Pages
• [Journal Article] Activation of NF-kB and implications for transformation. (2006)
  • Author(s): Sun S-C, *Yamaoka S
  • Journal Title: Oncogene 24 Pages: 5952-5964
• [Journal Article] Posttranslational modifications of NEMO and its partners in NF-kappaB signaling (2006)
  • Author(s): Helene Sebbanほか
  • Journal Title: Trends Cell Biol. 16 Pages: 569-577
• [Journal Article] Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling (2006)
  • Author(s): Masahiro Yamamotoほか
  • Journal Title: Nature Immunology 7 Pages: 962-970
• [Journal Article] Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isoinerase Pin1 (2006)
  • Author(s): Tatsuya Saitohほか
  • Journal Title: Nature Immunology 7 Pages: 598-605
• [Journal Article] An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappaB activation (2006)
  • Author(s): Tao Haiほか
  • Journal Title: J. Virology 80 Pages: 4227-4241
• [Journal Article] Distinct IkappaB kinase regulation in adult T cell leukemia and HTLV-I-transformed cells. (2005)
  • Author(s): Miura H, Maeda M, Yamamoto N, *Yamaoka S.
  • Journal Title: Exp Cell Res. 308 Pages: 29-40
• [Journal Article] Aberrant NF-kB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts. (2005)
  • Author(s): Nonaka, M., Hohrie, R., Itoh, K., Watanabe, T., Yamamoto, N., *Yamaoka S.
  • Journal Title: Oncogene 24 Pages: 3976-3986
• [Journal Article] A20 Is a Negative Regulator of Interferon Regulatory Factor 3 Signaling. (2005)
  • Author(s): Saitoh, T., Yamamoto, M., Miyagishi, M., Taira, K., Nakanishi, M., Fujita, T., Akira, S., Yamamoto, N., *Yamaoka S
  • Journal Title: J. Immunol. 174 Pages: 1507-12
• [Journal Article] Aberrant NF-kappaB2/p52 expression in Hodokin/Reedsternberg cells and CD30-transformed rat fibroblasts. (2005)
  • Author(s): 野中瑞穂 ほか
  • Journal Title: Oncogene 第24巻 Pages: 3976-3986
• [Journal Article] Distinct IkappaB kinase regulation in adult T cell leukemia and HTLV-I-transformed cells (2005)
  • Author(s): 三浦英靖 ほか
  • Journal Title: Experimental Cell Research 第308巻 Pages: 29-40
• [Journal Article] Upregulation of MUC6 mucin gene expression by NF-kappaB and Sp factors. (2005)
  • Author(s): Sakai H ほか
  • Journal Title: Biochemical and Biophysical Research Communications 第333巻 Pages: 1254-1260
• [Journal Article] Activation of NF-kappaB by HTLV-I an implications for cell transformation. (2005)
  • Author(s): Shao-Cong Sun ほか
  • Journal Title: Oncogene 第24巻 Pages: 5952-5964
• [Journal Article] Overexpression of NF-κB Inducing Kinase Underlies Constitutive NF-κB Activation in Lung Cancer Cells.
  • Author(s): Saitoh, Y., Martinez Bruyn, V.J., Uota, S., Hasegawa, A., Yamamoto, N., Imoto, I., Inazawa, J., *Yamaoka, S.
  • Journal Title: Lung Cancer (in press)
• [Journal Article] Efficient induction of HIV-1 replication in latently infected cells through contact with CD4+ T cells: involvement of NF-kappaB activation.
  • Author(s): Qi, X., Y. Koya, T. Saitoh, Y. Saitoh, S. Shimizu, K. Ohba, N. Yamamoto, *Yamaoka S.
  • Journal Title: Virology. 361 Pages: 325-33
• [Presentation] EBV膜タンパク質LMP1は、NF-kB inducing kinaseプロモーターの活性化を誘導する (2009)
  • Author(s): 斉藤愛記, 他
  • Organizer: 第57回ウイルス学会学術集会
  • Place of Presentation: 東京
• [Presentation] スタチンは成人T細胞白血病由来細胞株の蛋白質プレニル化を抑制し、その生育を阻害する (2009)
  • Author(s): 魚田慎, 他
  • Organizer: 第57回ウイルス学会学術集会
  • Place of Presentation: 東京
• [Presentation] HTLV-1 Taxによるp100プロセッシングに機能的NIKは必要でない (2009)
  • Author(s): 山岡昇司, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] EBV膜タンパク質LMP1は、NF-kB inducing kinase プロモーターの活性化を誘導する (2009)
  • Author(s): 斉藤愛記, 他
  • Organizer: 第57回ウイルス学会
  • Place of Presentation: 東京都市センターホテル
• [Presentation] スタチンは成人T細胞白血病由来細胞株の蛋白質プレニル化を抑制し、その生育を阻害する (2009)
  • Author(s): 魚田慎, 他
  • Organizer: 第57回ウイルス学会
  • Place of Presentation: 東京都市センターホテル
• [Presentation] HTLV-1 Taxによるp100プロセッシングに機能的NIKは必要でない (2009)
  • Author(s): 山岡昇司, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] 乳癌細胞における恒常的なNF-kBの活性化に対するNIKおよびA20の役割 (2009)
  • Author(s): 斉藤愛記, 他
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] Mechanism of constitutive NF-kappaB activation in cancer cells (2009)
  • Author(s): 斎藤愛記, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] RB-deficient cancer cells have deregulated E2F activity that activates tumor suppressor genes (2009)
  • Author(s): 大園瑛子, 他
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] NF-κBによるNIKプロモーター活性化 (2008)
  • Author(s): 山岡昇司、矢田沙和子、稲垣好雄、宮森久幸
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] 抗レトロウイルス治療中のガーナ人HIV感染者における血中ウイルス量の解析 (2008)
  • Author(s): 山岡昇司、山本典生
  • Organizer: 第22回日本エイズ学会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2008-11-26
• [Presentation] 癌細胞におけるNIKの異常発現による恒常的NF-kappaB活性化 (2008)
  • Author(s): 山岡昇司
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] 肺癌細胞株におけるNF-κ-B inducing kinase過剰発現によるNF-κB活性化 (2008)
  • Author(s): 斉藤愛記、山本直樹、山岡昇司
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-10-28
• [Presentation] TaxによるNF-κB inducing kinaseプロモーターの活性化 (2008)
  • Author(s): 面岡昇司、稲垣好雄、宮森久幸、斎藤愛記
  • Organizer: 第1回HTLV-I研究会・合同班会議
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2008-08-02
• [Presentation] 成人T細胞白血病(ATL)細胞におけるNF-κB inducing kinase(NIK)の発現上昇機構 (2008)
  • Author(s): 斉藤愛記、井本逸勢、稲澤譲治、宇都宮與、渡邉俊樹、山本直樹、山岡昇司
  • Organizer: 第1回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2008-08-02
• [Presentation] TaxによるNF-κB inducing kinaseプロモーターの活性化 (2008)
  • Author(s): 山岡昇司, 他
  • Organizer: 第1回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京
• [Presentation] NF-κBによるNIKプロモーター活性化 (2008)
  • Author(s): 山岡昇司, 他
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 名古屋
• [Presentation] 成人T細胞白血病(ATL)細胞におけるNF-κB inducing kinase (NIK)の発現上昇機構 (2008)
  • Author(s): 斉藤愛記, 他
  • Organizer: 第1回HTLV-1研究会・合同班会議
  • Place of Presentation: 東京
• [Presentation] 恒常的NF-kappaB活性化と悪性腫瘍 (2007)
  • Author(s): 山岡昇司
  • Organizer: 日本分子生物学会生化学会合同総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] HTLV-1 taxによるNIK遺伝子転写制御機構 (2007)
  • Author(s): 宮森久幸, 斉藤愛記、山本直樹、山岡昇司
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] 恒常的NF-kappaB活性化と悪性腫瘍。 (2007)
  • Author(s): 山岡昇司
  • Organizer: BMB2007ワークショップ
  • Place of Presentation: 横浜
• [Presentation] HTLV-1 taxによるNIK遺伝子転写制御機構 (2007)
  • Author(s): 宮森久幸, 他
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] ATL細胞株におけるNIKの過剰発現は恒常的NF-κB活性化およびマウスにおける腫瘍形成に関与する (2007)
  • Author(s): 斉藤愛記, 他
  • Organizer: 第55回ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] IKK阻害剤IMD-0354はEBV感染不死化B細胞(LCL)の増殖を抑制する (2007)
  • Author(s): 魚田慎, 他
  • Organizer: 第55回ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] HTLV-I感染細胞におけるSTAT3の発現抑制に伴う細胞増殖抑制 (2006)
  • Author(s): 堀内三吉, 他
  • Organizer: 第55回日本ウイルス学会学術集会
  • Place of Presentation: 札幌
• [Presentation] 転写因子NF-κBの新規阻害剤IMD-0354はATL細胞の増殖を抑制し細胞死を誘導 (2006)
  • Author(s): 魚田慎, 他
  • Organizer: 第54回日本ウイルス学会集会
  • Place of Presentation: 名古屋
• [Presentation] IKK阻害剤IMD-0354のATL細胞増殖抑制効果。 (2005)
  • Author(s): 野中瑞穂, 他
  • Organizer: 第53回日本ウイルス学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Statin系薬剤はAdult T cell leukemia (ATL)細胞株の増殖を抑制する。 (2005)
  • Author(s): 山岡昇司, 他
  • Organizer: 第64回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Remarks]
  • URL: http://www.tmd.ac.jp/med/mmb/Home.htm