Informatory expression system connecting cancer and immunity.

2009 Fiscal Year Final Research Report

• Project/Area Number: 17012005
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: TANIGUCHI Tadatsugu The University of Tokyo, 大学院・医学系研究科, 教授 (50133616)
• Co-Investigator(Kenkyū-buntansha): TAKAOKA Akinori 北海道大学, 遺伝子病制御研究所, 教授 (30323611) ; TAMURA Tonohiko 東京大学, 大学院・医学系研究科, 准教授 (50285144) ; HONDA Kenya 東京大学, 大学院・医学系研究科, 助手 (60334231) ; OOBA Yuusuke 東京大学, 大学院・医学系研究科, 助手 (30333503) ; YANAI Hideyuki 東京大学, 大学院・医学系研究科, 助教 (70431765)
• Project Period (FY): 2005 – 2009
• Keywords: インターフェロン / IRFファミリー / p53 / 樹状細胞 / 発がん抑制 / Noxa / Puma / Toll様受容体

Research Abstract

We investigated biological mechanisms and role of effecter molecules, e.g. interferons, IRFs and Noxa. It revealed that these molecules are involved in transformation, apoptosis induction and metastasis signaling pathways. We also found the cross-talk pathway between TLRs signaling. Moreover, we identified DAI and HMGB1, 2, 3 are important for the nucleic-acid mediated innate immune responses. Since these pathways regulate tumorgenesis and exacerbation, our findings will be proved to be useful for the development of novel tumor therapy in near future.

Research Products

• [Journal Article] Regulation of immunity and oncogenesis by the IRF transcription factor family. (2010)
  • Author(s): Savitsky D, Tamura T, Yanai H, Taniguchi T.
  • Journal Title: Cancer Immunol. Immunother. Vol.59 Pages: 489-510
  • Peer Reviewed
• [Journal Article] HMGB proteins function as universal sentinels for nucleic acid-mediated innate immune responses. (2009)
  • Author(s): Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani R, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T.
  • Journal Title: Nature Vol.462 Pages: 99-103
  • Peer Reviewed
• [Journal Article] A selective contribution of the RIG-I-like receptor pathway to type I interferon responses activated by cytosolic DNA. (2009)
  • Author(s): Choi MK, Wang Z, Ban T, Yanai H, Lu Y, Koshiba R, Nakaima Y, Hangai S, Savitsky D, Nakasato M, Negishi H, Takeuchi O, Honda K, Akira S, Tamura T, Taniguchi T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.106 Pages: 17870-17875
  • Peer Reviewed
• [Journal Article] Cell type-dependent proapoptotic role of Bcl2L12 revealed by a mutation concomitant with the disruption of the juxtaposed Irf3 gene. (2009)
  • Author(s): Nakajima A, Nishimura K, Nakaima Y, Oh T, Noguchi S, Taniguchi T, Tamura T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.106 Pages: 12448-12452
  • Peer Reviewed
• [Journal Article] Therapeutic potential of proapoptotic molecule Noxa in the selective elimination of tumor cells. (2009)
  • Author(s): Suzuki S, Nakasato M, Shibue T, Koshima I, Taniguchi T.
  • Journal Title: Cancer Sci. Vol.100 Pages: 759-769
  • Peer Reviewed
• [Journal Article] Critical role for constitutive type I interferon signaling in the prevention of cellular transformation. (2009)
  • Author(s): Chen HM, Tanaka N, Mitani Y, Oda E, Nozawa H, Chen JZ, Yanai H, Negishi H, Choi MK, Iwasaki T, Yamamoto H, Taniguchi T, Takaoka A.
  • Journal Title: Cancer Sci. Vol.100 Pages: 449-456
  • Peer Reviewed
• [Journal Article] Regulation of the cytosolic DNA-sensing system in innate immunity: a current view. (2009)
  • Author(s): Yanai H, Savitsky D, Tamura T, Taniguchi T.
  • Journal Title: Curr. Opin. Immunol. Vol.1 Pages: 17-22
  • Peer Reviewed
• [Journal Article] A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. (2008)
  • Author(s): Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T, Kaisho T, Taya C, Taniguchi T, Honda K.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.105 Pages: 20446-20451
  • Peer Reviewed
• [Journal Article] The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and T(H)1 versus T(H)-17 differentiation of CD4(+) T cells. (2008)
  • Author(s): Kano S, Sato K, Morishita Y, Vollstedt S, Kim S, Bishop K, Honda K, Kubo M, Taniguchi T.
  • Journal Title: Nat. Immunol. Vol.9 Pages: 34-41
  • Peer Reviewed
• [Journal Article] Interferon regulatory factor family of transcription factors and regulation of oncogenesis. (2008)
  • Author(s): Takaoka A, Tamura T, Taniguchi T.
  • Journal Title: Cancer Sci. Vol.99 Pages: 467-478
  • Peer Reviewed
• [Journal Article] Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. (2008)
  • Author(s): Mizutani T, Tsuji K, Ebihara Y, Taki S, Ohba Y, Taniguchi T, Honda K.
  • Journal Title: Exp. Hematol. Vol.36 Pages: 255-264
  • Peer Reviewed
• [Journal Article] A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis. (2008)
  • Author(s): Couzinet A, Tamura K, Chen HM, Nishimura K, Wang Z, Morishita Y, Takeda K, Yagita H, Yanai H, Taniguchi T, Tamura T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.105 Pages: 2556-2561
  • Peer Reviewed
• [Journal Article] The IRF Family Transcription Factors in Immunity and Oncogenesis. Annu. (2008)
  • Author(s): Tamura T, Yanai H, Savitsky D, Taniguchi T.
  • Journal Title: Rev. Immunol. Vol.26 Pages: 535-584
  • Peer Reviewed
• [Journal Article] Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules. (2008)
  • Author(s): Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.105 Pages: 5477-5482
  • Peer Reviewed
• [Journal Article] Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. (2007)
  • Author(s): Yanai H., Chen H., Inuzuka T., Kondo S., Mak WT., Takaoka A., Honda K. Taniguchi T.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.104 Pages: 3402-3407
  • Peer Reviewed
• [Journal Article] DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. (2007)
  • Author(s): Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T.
  • Journal Title: Nature Vol.448 Pages: 501-505
  • Peer Reviewed
• [Journal Article] Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism. (2007)
  • Author(s): Onoguchi K, Yoneyama M, Takemura A, Akira S, Taniguchi T, Namiki H, Fujita T.
  • Journal Title: J. Biol. Chem. Vol.282 Pages: 7576-7581
  • Peer Reviewed
• [Journal Article] Differential contribution of Puma and Noxa in dual regulation of p53-dependent apoptotic pathways. (2006)
  • Author(s): Shibue T, Suzuki S, Okamoto H, Yoshida H, Ohba Y, Takaoka A, Taniguchi T.
  • Journal Title: EMBO J. Vol.25 Pages: 4952-4962
  • Peer Reviewed
• [Journal Article] BH3-only proteins: Integrated control point of apoptosis. (2006)
  • Author(s): Shibue T, Taniguchi T.
  • Journal Title: Int. J. Cancer Vol.119 Pages: 2036-2043
  • Peer Reviewed
• [Journal Article] Evidence for licensing of IFN-γ-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. (2006)
  • Author(s): Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.103 Pages: 15136-15141
  • Peer Reviewed
• [Journal Article] IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. (2006)
  • Author(s): Honda K, Taniguchi T.
  • Journal Title: Nat. Rev. Immunol. Vol.6 Pages: 644-659
  • Peer Reviewed
• [Journal Article] Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. (2005)
  • Author(s): Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano S, Honda K, Ohba Y, Mak TM, Taniguchi T.
  • Journal Title: Nature Vol.434 Pages: 243-249
  • Peer Reviewed
• [Journal Article] IRF-7 is the master regulator of type-I interferon-dependent immune responses. (2005)
  • Author(s): Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T.
  • Journal Title: Nature Vol.434 Pages: 772-777
  • Peer Reviewed
• [Journal Article] Spatiotemporal regulation of MmyD88-IRF-7 signalling for robust type I interferon induction. (2005)
  • Author(s): Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, Takaoka A, Taya C, Taniguchi T.
  • Journal Title: Nature Vol.434 Pages: 1035-1040
  • Peer Reviewed
• [Journal Article] Negative regulation of Toll-like-receptor signaling by IRF-4. (2005)
  • Author(s): Negishi H, Ohba Y, Yanai H, Takaoka A, Honma K, Yui K, Matsuyama T, Taniguchi T, Honda K.
  • Journal Title: Proc. Natl. Acad. Sci. USA Vol.102 Pages: 15989-15994
  • Peer Reviewed
• [Journal Article] Type I interferon system and IRF family of transcription factors in host defense regulation. (2005)
  • Author(s): Taniguchi T, Takaoka A.
  • Journal Title: Proc. Jpn. Acad. Vol.81 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Regulation of the type I IFN induction: a current view. (2005)
  • Author(s): Honda K, Yanai H, Takaoka A, Taniguchi T.
  • Journal Title: Int. Immunol. Vol.17 Pages: 1367-1378
  • Peer Reviewed
• [Presentation] Nucleic acid sensing and activation of innate and adaptive immune responses. (2010)
  • Author(s): Taniguchi T.
  • Organizer: World Immune Regulation Meeting IV
  • Place of Presentation: Davos, Switzerland
  • Year and Date: 20100329-20100401
• [Presentation] Nucleic Acids-Sensing, Signaling and IRF Transcription Factors in Inflammation and Immunity. (2009)
  • Author(s): Taniguchi T.
  • Organizer: The 9th World Congress on Inflammation
  • Place of Presentation: 東京
  • Year and Date: 20090706-20090710
• [Presentation] Nucleic Acids Sensing, IRFs and Interferons: Implication in Protective and Pathological Immunities. (2009)
  • Author(s): Taniguchi T.
  • Organizer: 米国臨床免疫学講座学会
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20090611-20090614
• [Presentation] Activation of innate immune responses by nucleic acids and IRFs. (2009)
  • Author(s): Taniguchi T.
  • Organizer: Immune Regulation
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 20090525-20090527
• [Presentation] Sencing, signaling and transcription in the innate immune response (2008)
  • Author(s): Taniguchi T.
  • Organizer: The 6th Congress of the Chinese Society for Immunology
  • Place of Presentation: 西安、中華人民共和国
  • Year and Date: 20081031-20081103
• [Presentation] Cytoplasmic receptors for the perception of danger (2008)
  • Author(s): Taniguchi T.
  • Organizer: 1st International Conference on Immunochemotherapy
  • Place of Presentation: Paris, France
  • Year and Date: 20081017-20081018
• [Presentation] 30 Years After the Dawn of Cytokine Molecular Biology: Roles of IRF Transcription Factors (2008)
  • Author(s): Taniguchi T.
  • Organizer: Cytokines 2008-7th Joint Conference of the International Society for Interferon and Cytokine Research and International Cytokine Society
  • Place of Presentation: モントリオール(カナダ)
  • Year and Date: 20081012-20081016
• [Presentation] Regulation of Innate Immune Responses by DAI (DLM-1/ ZBP1) and Other DNA-semsing Molecules. (2008)
  • Author(s): Wang Z., et al.
  • Organizer: 7th Joint Conference of the International Society for Interferon and Cytokine Research and International Cytokine Society
  • Place of Presentation: モントリオール(カナダ)
  • Year and Date: 20081012-20081016
• [Presentation] 核酸認識による免疫系の活性化. (2008)
  • Author(s): Taniguchi T.
  • Organizer: Toll 2008国際会議
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 20080824-20080827
• [Presentation] The IRF family transcription factors in oncogenes and immunity. (2008)
  • Author(s): Taniguchi T.
  • Organizer: Molecular biology of cancer: 20 years of progress punctuated by the Pezcoller Symposia
  • Place of Presentation: in Trento, Italy
  • Year and Date: 20080611-20080613
• [Presentation] Senseing, signaling and transcription in innate immune responses. (2008)
  • Author(s): Taniguchi T.
  • Organizer: 1st International-Singapore Symposium of Immunology
  • Place of Presentation: Biopolis, Singapore
  • Year and Date: 20080112-20080116
• [Presentation] Interferons and DNA Sensors (2008)
  • Author(s): Taniguchi T.
  • Organizer: Perspectives in Immunology Symposium
  • Place of Presentation: California, USA
  • Year and Date: 2008-05-12
• [Presentation] IRF-5の抗ウイルス応答及び抗腫瘍応答における役割 (2007)
  • Author(s): 柳井秀元.
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 20071003-20071005
• [Presentation] IRFs in Innate Immune Signaling. (2007)
  • Author(s): Taniguchi T.
  • Organizer: Interacademy Symposium: innate immunity and its interface with adaptive immunity
  • Place of Presentation: France
  • Year and Date: 20070802-20070805
• [Presentation] Regulation of immune response and tumor suppression by the IRF family transcription factors. (2007)
  • Author(s): Taniguchi T.
  • Organizer: International Conference on Immunology
  • Place of Presentation: China
  • Year and Date: 20070712-20070715
• [Patent(Industrial Property Rights)] 核酸により活性化される自然免疫応答の抑制剤およびそのスクリーニング方法
  • Inventor(s): 谷口維紹
  • Industrial Property Rights Holder: 谷口維紹
  • Industrial Property Number: 特許・特願2009-238606