Viral oncogenesis and NF-kappaB

2009 Fiscal Year Final Research Report

• 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

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] 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] 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] 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
  • URL: doi:10.1038/mp.a000159.01
• [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] 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] 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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20091000
• [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
  • Year and Date: 20081200
• [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
  • Year and Date: 20080800
• [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
  • Year and Date: 20080800
• [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
  • Year and Date: 20071100
• [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
  • Year and Date: 20071000
• [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
  • Year and Date: 20071000
• [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
  • Year and Date: 20071000
• [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
  • Year and Date: 20061100
• [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
  • Year and Date: 20061100
• [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
  • Year and Date: 20051100
• [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
  • Year and Date: 20050900
• [Remarks]
  • URL: http://www.tmd.ac.jp/med/mmb/Home.htm