Molecular mechanisms of abnormal differentiation and transcriptional regulation in cancer cel

• Project/Area Number: 17014017
• 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: INOUE Jun-ichiro The University of Tokyo, 医科学研究所, 教授 (70176428)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥50,200,000 (Direct Cost: ¥50,200,000); Fiscal Year 2009: ¥10,100,000 (Direct Cost: ¥10,100,000); Fiscal Year 2008: ¥10,100,000 (Direct Cost: ¥10,100,000); Fiscal Year 2007: ¥10,100,000 (Direct Cost: ¥10,100,000); Fiscal Year 2006: ¥10,100,000 (Direct Cost: ¥10,100,000); Fiscal Year 2005: ¥9,800,000 (Direct Cost: ¥9,800,000)
• Keywords: 癌 / シグナル伝達 / 発現制御 / 発生・分化 / ウイルス発癌 / ウィルス発癌 / 発生制御 / 白血病 / NFκB / TRAF6 / HTLV-1 / Tax

Research Abstract

We aimed to clarify molecular mechanisms of the TRAF6-mediated NF-κB activation and roles of NF-κB in oncogenesis and malignancy. The following results were obtained. (1)Oncogenic Tax protein of HTLV-1 activates NF-κB to induce dysregulated cell growth. In contrast to the cytokine-induced NF-κB activation, our results strongly suggest that Tax-mediated NF-κB activation does not require TAK1 and K63-linked polyubiquitination of NEMO. Based on these results we propose a novel model of NF-κB activation by Tax. (2)Enhanced expression of IL-1 is involved in malignancy of cancer. We found that IL-1 stimulation results in TRAF6-catalyzed K63-linked polyubiquitination of TAK1, which is essential for TAK1 activation. We further found that MEKK3 is an essential upstream activator of TAK1, and TRAF6, MEKK3 and TAK1 form signal complexes in an IL-1 stimulation-dependent manner. We propose the biphasic NF-κB activation model, in which the TAK1-dependent RING pathway precedes the TAK1-independent Zinc pathway. (3)We identified 25 NF-κB target genes that probably involved in cancer malignancy. (4)Six cell lines derived from breast, lung and gastric cancers, whose growth depends on NF-kB activation, grow in an IKKα-dependent manner. The result suggests involvement of the non-classical pathway in their proliferation.

Research Products

• [Journal Article] Human lactoferrin activates NF-κB through Toll-like receptor 4 (TLR4) pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling. (2010)
  • Author(s): Ando, K., Hasegawa, K., Shindo, K., Furusawa, T., Fujino, T., Kikugawa, K., Nakano, H., Takeuchi, O., Akira, S., Akiyama, T., Gohda, J., Inoue, J., Hayakawa, M.
  • Journal Title: FEBS Journal (in press)
• [Journal Article] Human lactoferrin activates NF-κB through Toll-like receptor 4(TLR4)pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling (2010)
  • Author(s): Ando, K.
  • Journal Title: FEBS Journal (in press)
  • Peer Reviewed
• [Journal Article] Temporal perturbation of tyrosine-phosphoproteome dynamics reveals the system-wide regulatory networks. (2009)
  • Author(s): Oyama, M., Kozuka-Hata, H, Tasaki, S., Semba, K., Hattori, S., Sugano, S., Inoue, J., Yamamoto, T.
  • Journal Title: Mol. Cell. Proteomics 8 Pages: 226-231
• [Journal Article] Selective transmission of R5 HIV-1 over X4 HIV-1 at the dendritic cell-T cell infectious synapse is determined by the T cell activation state. (2009)
  • Author(s): Yamamoto, T., Yokota, Y., Mitsuki, Y., Mizukoshi, F., Tsuchiya, T., Terahara, K., Inagaki, Y., Yamamoto, N., Kobayashi, K., Inoue, J.
  • Journal Title: PLos Pathogens 5(1)
• [Journal Article] Predicting Novel Features of Toll-Like Receptor 3 Signaling in Macrophages. (2009)
  • Author(s): Helmy, M., Gohda, J., Inoue, J., Tomita, M., Tsuchiya, M., Selvarajoo K.
  • Journal Title: PLoS ONE 4(3)
• [Journal Article] TRAF6 Establishes Innate Immune Responses by Activating NF-κB and IRF7 upon Sensing Cytosolic Viral RNA and DNA. (2009)
  • Author(s): Konno, H., Yamamoto, T., Yamazaki, K., Gohda, J., Akiyama, T., Semba, K., Goto, H., Kato, A, Yujiri, T, Imai, T., Kawaguchi, Y., Su, B., Takeuchi, O., Akira, S., Tsunetsugu-Yokota, Y., Inoue, J.
  • Journal Title: PLoS ONE 4(5)
• [Journal Article] Constitutive activation of NF-κB is preferentially involved in the proliferation of basal-like subtype breast cancer cell lines. (2009)
  • Author(s): Yamaguchi, N., Ito, T., Azuma, S., Ito, E., Honma, R., Yanagisawa, Y., Nishikawa, A., Kawamura, M., Imai, J., Watanabe, S., Semba, K., Inoue, J.
  • Journal Title: Cancer Sci. 100 Pages: 1668-1674
• [Journal Article] TRAF-interacting protein with a forkhead-associated domain B (TIFAB) is a negative regulator of the TRAF6-induced cellular functions. (2009)
  • Author(s): Matsumura, T., Kawamura-Tsuzuku, J., Yamamoto, T., Semba, K., Inoue, J.
  • Journal Title: J. Biochem. 146 Pages: 375-381
  • NAID: 10026303311
• [Journal Article] NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells. Biochem. Biophys. (2009)
  • Author(s): Nishina, T., Yamaguchi, N., Gohda, J., Semba, K., Inoue, J.
  • Journal Title: Res. Commun. 388 Pages: 96-101
• [Journal Article] A unique domain in RANK is required for Gab2 and PLCγ2 binding to establish osteoclastogenic signals. (2009)
  • Author(s): Taguchi, Y., Gohda, J., Koga, T., Takayanagi, H., Inoue, J.
  • Journal Title: Genes Cells 14 Pages: 1331-1345
• [Journal Article] Two Mechanistically and Temporally Distinct NF-κB Activation Pathways in IL-1 Signaling. (2009)
  • Author(s): Yamazaki, K., Gohda, J., Kanayama, A., Miyamoto, Y., Sakurai, H., Yamamoto, M., Akira, S., Hayashi, H., Su, B., Inoue, J.
  • Journal Title: Sci. Signal. 2
• [Journal Article] Independent stabilizations of polysomal Drg1/Dfrp1 complex and non-polysomal Drg2/Dfrp2 complex in mammalian cells. (2009)
  • Author(s): Ishikawa, K., Akiyama, T., Ito, K., Semba, K., Inoue, J.
  • Journal Title: Biochem. Biophys. Res. Commun. 390 Pages: 552-556
• [Journal Article] Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity. (2009)
  • Author(s): Nagatake, T., Fukuyama, S., Kim, D.Y., Goda, K., Igarashi, O., Sato, S., Nochi, T., Sagara, H., Yokota, Y., Jetten, A.M., Kaisho, T., Akira, S., Mimuro, H., Sasakawa, C., Fukui, Y., Fujihashi, K., Akiyama, T., Inoue, J., Penninger, J.M., Kunisawa, J., Kiyono, H.
  • Journal Title: J Exp Med. 206 Pages: 2351-2364
• [Journal Article] TRAF6 Establishes Innate Immune Responses by Activating NF-κB and IRF7 upon Sensing Cytosolic Viral RNA and DNA (2009)
  • Author(s): Konno, H.
  • Journal Title: PLoS ONE 4(5)
  • Peer Reviewed
• [Journal Article] Constitutive activation of NF-κB is preferentially involved in the proliferation of basal-like subtype breast cancer cell lines (2009)
  • Author(s): Yamaguchi, N.
  • Journal Title: Cancer Sci 100 Pages: 1668-1674
  • Peer Reviewed
• [Journal Article] TRAF-interacting protein with a forkhead-associated domain B(TIFAB)is a negative regulator of the TRAF6-induced cellular functions (2009)
  • Author(s): Matsumura, T.
  • Journal Title: J.Biochem 146 Pages: 375-381
  • Peer Reviewed
• [Journal Article] NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells (2009)
  • Author(s): Nishina, T.
  • Journal Title: Biochem.Biophys.Res.Commun. 388 Pages: 96-101
  • Peer Reviewed
• [Journal Article] A unique domain in RANK is required for Gab2 and PLCγ2 binding to establish osteoclastogenic signals (2009)
  • Author(s): Taguchi, Y.
  • Journal Title: Genes Cells 14 Pages: 1331-1345
  • Peer Reviewed
• [Journal Article] Two Mechanistically and Temporally Distinct NF-κB Activation Pathways in IL-1 Signaling (2009)
  • Author(s): Yamazaki, K.
  • Journal Title: Sci.Signal 2
  • Peer Reviewed
• [Journal Article] Independent stabilizations of polysomal Drg1/Dfrp1 complex and non-polysomal Drg2/Dfrp2 complex in mammalian cells (2009)
  • Author(s): Ishikawa, K.
  • Journal Title: Biochem.Biophys.Res.Commun 390 Pages: 552-556
  • Peer Reviewed
• [Journal Article] Penninger, J.M., Kunisawa, J., Kiyono, H.Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity (2009)
  • Author(s): Nagatake, T.
  • Journal Title: J Exp Med 206 Pages: 2351-2364
  • Peer Reviewed
• [Journal Article] Temporal perturbation of tyrosine-phosphoproteome dynamics reveals the system-wide regulatory networks (2009)
  • Author(s): Oyama, M.
  • Journal Title: Mol. Cell. Pro teomics 8 Pages: 226-231
  • Peer Reviewed
• [Journal Article] Selective transmission of R5 HIV-1 over X4 HIV-1 at the de dritic cell-T cell infectious synapse is determined by the T cell activation state (2009)
  • Author(s): Yamamoto, T.
  • Journal Title: PLos Pathogens 5(1) Pages: 1000279-1000279
  • Peer Reviewed
• [Journal Article] Predicting Novel Features of Toll-Like Receptor 3 Signaling in Macrophages (2009)
  • Author(s): Helmy, M.
  • Journal Title: PLoS ONE (in press)
  • Peer Reviewed
• [Journal Article] FoxA1 as a lineage-specific oncogene in luminal type breast cancer. Biochem. (2008)
  • Author(s): Yamaguchi, N., Ito, E., Azuma, S., Honma, R., Yanagisawa, Y., Nishikawa, A., Kawamura, M., Imai, J., Tatsuta, K., Inoue, J., Semba, K., Watanabe, S.
  • Journal Title: Biophys. Res. Commun 365 Pages: 711-717
• [Journal Article] NOTCH3 signaling pathway plays crucial roles in proliferation of ErbB2-negative human breast cancer cells. (2008)
  • Author(s): Yamaguchi, N., Oyama T, Ito E, Satoh H, Azuma S, Hayashi M, Shimizu K, Honma R, Yanagisawa Y, Nishikawa A, Kawamura M, Imai J, Ohwada S, Tatsuta K, Inoue J, Semba K, Watanabe S.
  • Journal Title: Cancer Res. 68 Pages: 1881-1888
• [Journal Article] Interaction of anti-proliferative protein Tob with the CCR4-NOT deadenylase complex. (2008)
  • Author(s): Miyasaka, T., Morita, M., Ito, K., Suzuki, T., Fukuda, H., Takeda, S., Inoue, J., Semba, K., Yamamoto, T.
  • Journal Title: Cancer Sci. 99 Pages: 755-761
  • NAID: 10024005002
• [Journal Article] The Tumor Necrosis Factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. (2008)
  • Author(s): Akiyama T., Shimo Y., Yanai H., Qin J., Ohsima, D., Maruyama Y., Asaumi Y., Kitazawa J., Takayanagi H., Penninger JM., Matsumoto M., Nitta T., Takahama Y., Inoue J.
  • Journal Title: Immunity 29 Pages: 423-437
• [Journal Article] The Cytokine RANKL Produced by Positively Selected Thymocytes Fosters Medullary Thymic Epithelial Cells that Express Autoimmune Regulator. (2008)
  • Author(s): Hikosaka Y., Nitta T., Ohigashi I., Yano K., Ishimaru N., Hayashi Y., Matsumoto M., Matsuo K., Penninger JM., Takayanagi H., Yokota Y., Yamada H., Yosikai Y., Inoue J., Akiyama T., Takahama Y.
  • Journal Title: Immunity 29 Pages: 438-450
• [Journal Article] TRAF6 specifically contributes to FcεRI-mediated cytokine production but not mast cell degranulation. (2008)
  • Author(s): Yang Y.J., Chen W., Carrigan S.O., Chen W-M., Roth K., Akiyama T., Inoue J., Marshall J.S., Berman J.N., Lin Y-J.
  • Journal Title: J. Biol. Chem. 283 Pages: 32110-32118
• [Journal Article] Signaling Flux Redistribution at Toll-like Receptor Pathway Junctions. (2008)
  • Author(s): Selvarajoo, K, Takada, Y, Gohda, J., Helmy, M., Akira, S., Tomita, M., Tsuchiya, M., Inoue, J., Matsuo, K.
  • Journal Title: PLoS ONE 3(10)
• [Journal Article] The Tumor Necrosis Factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and .self-tolerance. (2008)
  • Author(s): Akiyama T.
  • Journal Title: Immunity 29 Pages: 423-437
  • Peer Reviewed
• [Journal Article] The Cytokine RANKL Produced by Positively Selected Thymocytes Fosters Medullary Thymic Epithelial Cells that Express Autoimmune Regulator (2008)
  • Author(s): Hikosaka Y.
  • Journal Title: Immunity 29 Pages: 438-450
  • Peer Reviewed
• [Journal Article] Marshall J.S., Berman J.N. and Lin Y-J. TRAF6 specifically contributes to FcERI-mediated cytokine production but not mast cell degranulation (2008)
  • Author(s): Yang Y.J.
  • Journal Title: J. Biol. Chem. 283 Pages: 32110-3211
  • Peer Reviewed
• [Journal Article] Signaling Flux Redistribution at Toll-like Receptor Pathway Junctions (2008)
  • Author(s): Selvarajoo, K
  • Journal Title: PLoS ONE 3 (10) Pages: 3430-3430
  • Peer Reviewed
• [Journal Article] FoxAl as a lineage-specific oncogene in luminal type breast cancer. (2008)
  • Author(s): Yamaguchi, N.
  • Journal Title: Biochem. Biophys. Res. Commun 365 Pages: 711-717
  • Peer Reviewed
• [Journal Article] NOTCH3 signaling pathway plays crucial roles in proliferation of ErbB2-negative human breast cancer cells. (2008)
  • Author(s): Yamaguchi, N.
  • Journal Title: Cancer Res. 68 Pages: 1881-1888
  • Peer Reviewed
• [Journal Article] Interaction of anti-proliferative protein Tob with the CCR4-NOT deadenylase complex. (2008)
  • Author(s): Miyasaka, T.
  • Journal Title: Cancer Sci. 99 Pages: 755-761
  • Peer Reviewed
• [Journal Article] NF-κB activation in development and progression of cancer. (2007)
  • Author(s): Inoue, J., Gohda, J., Akiyama, T., Semba, K.
  • Journal Title: (review) Cancer Sci. 98 Pages: 268-274
  • NAID: 10019481113
• [Journal Article] HTLV-1 Tax-induced NFκB activation is independent of Lys-63-linked-type polyubiquitination, Biochem. (2007)
  • Author(s): Gohda, J., Irisawa, M., Tanaka, Y., Sato, S., Ohtani, K., Fujisawa, J., Inoue, J.
  • Journal Title: Biophys. Res. Commun. 357 Pages: 225-30
• [Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast cancers. (2007)
  • Author(s): Ito, E., Honma, R., Yanagisawa, Y., Imai, J., Azuma, S., Oyama, T., Ohwada, S., Akiyama, T., Nomura, N., Inoue, J., Watanabe, S., Semba, K.
  • Journal Title: FEBS Letter 581 Pages: 3909-3914
• [Journal Article] Developmental stage-dependent collaboration between the TRAF6 and lymphotoxin pathways for B-cell follicle organization in secondary lymphoid organs. (2007)
  • Author(s): Qin, J., Konno, H., Ohshima, D., Yanai, H., Motegi, H., Hirota, F., Matsumoto, M., Takaki, S., Inoue, J., Akiyama, T.
  • Journal Title: J. Immunol. 179 Pages: 6799-6807
• [Journal Article] NF-κB activation in development and progression of cancer. (2007)
  • Author(s): Inoue, J.
  • Journal Title: Cancer Sci. 98 Pages: 268-274
  • NAID: 10019481113
  • Peer Reviewed
• [Journal Article] HTLV-1 Tax-induced NF κB activation is independent of Lys-63-linked-type polyubiquitination (2007)
  • Author(s): Gohda, J.
  • Journal Title: Biochem. Biophys. Res. Commun. 357 Pages: 225-230
  • Peer Reviewed
• [Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast cancers (2007)
  • Author(s): Ito, E.
  • Journal Title: FEBS Letter 581 Pages: 3909-3914
  • Peer Reviewed
• [Journal Article] Developmental stage-dependent collaboration between the TRAF6 and lymphotoxin pathways for B-cell follicle organization in secondary lymphoid organs (2007)
  • Author(s): Qin, J.
  • Journal Title: J. Immunol. 179 Pages: 6799-6807
  • Peer Reviewed
• [Journal Article] NF-κ B activation in development and progression of cancer. (2007)
  • Author(s): Inoue J
  • Journal Title: Cancer Sci. 98 Pages: 268-274
  • NAID: 10019481113
• [Journal Article] HTLV-1 Tax-induced NF κ B activation is independent of Lys-63-linked-type polyubiquitination. (2007)
  • Author(s): Gohda J
  • Journal Title: Biochem. Biophys. Res. Commun. 357 Pages: 225-230
• [Journal Article] Involvement of TNF Receptor-associated Factor (TRAF) 6 in IL-25 Receptor Signaling. (2006)
  • Author(s): Maezawa, Y., Nakajima, H., Suzuki, K., Tamachi, T., Ikeda, K., Inoue, J., Saito, Y., Iwamoto, I.
  • Journal Title: J Immunol. 176 Pages: 1013-1018
• [Journal Article] Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion formation in a stent implantation model of rabbit carotid artery. (2006)
  • Author(s): Miyahara, T., Koyama, H., Miyata, T., Shigematsu, H., Inoue, J., Takato, T., Nagawa, H.
  • Journal Title: J. Vasc. Surg. 43 Pages: 592-600
• [Journal Article] Characteristics and Biological Functions of TRAF6. In "TRAFs" edited by Hao Wu. (2006)
  • Author(s): Inoue, J., Gohda, J., Akiyama, T.
  • Journal Title: Landes Bioscience, Adv Exp Med Biol 597 Pages: 72-79
• [Journal Article] Biological evaluation, chelation and molecular modeling studies of novel metal-chelating inhibitors of NF-κB-DNA binding: Structure activity relationship. (2006)
  • Author(s): Sharma, R.K., Chopra, S., Sharma, S.D., Pande, V., Ramos, M.J., Meguro, K., Inoue, J., Otsuka, M.
  • Journal Title: J. Med. Chem 49 Pages: 3595-601
• [Journal Article] IL-18 produced by thymic epithelial cells induces development of dendritic cells with CD11b in the fetal thymus. (2006)
  • Author(s): Ito, H., Esashi, E., Akiyama, T., Inoue, J., Miyajima, A.
  • Journal Title: Int. Immunol. 18 Pages: 1253-1263
  • NAID: 10018773162
• [Journal Article] Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping region of HIV nef inhibit HIV replication and infectivity in primary macrophages. (2006)
  • Author(s): Yamamoto, T., Miyoshi, H., Yamamoto, N., Yamamoto, N., Inoue, J., Tsunetsugu-Yokota, Y.
  • Journal Title: Blood 108 Pages: 3305-3312
• [Journal Article] TNF-receptor associated factor 6-deficient fibroblast is sensitive to the TNF-alpha-induced cell death: Involvement of reactive oxygen species. (2006)
  • Author(s): Ichikawa, D., Funakoshi-Tago, M., Aizu-Yokota, E., Sonoda, Y., Inoue, J., Kasahara T.
  • Journal Title: Biochem Biophys Res Commun. 351 Pages: 93-98
• [Journal Article] Involvement of TNF Receptor-associated Factor (TRAF) 6 in IL-25 Receptor Signaling. (2006)
  • Author(s): Maezawa Y
  • Journal Title: J Immunol. 176 Pages: 1013-1018
• [Journal Article] Biological evaluation, chelation and molecular modeling studies of novel metal-chelating inhibitors of NF-κ B-DNA binding : Structure activity relationship. (2006)
  • Author(s): Sharma RK
  • Journal Title: J. Med. Chem 33 Pages: 67-81
• [Journal Article] IL-18 produced by thymic epithelial cells induces development of dendritic cells with CD11b in the fetal thymus. (2006)
  • Author(s): Ito H
  • Journal Title: Int. Immunol. 18 Pages: 1253-1263
• [Journal Article] Lentivirus vectors expressing short hairpin RNAs against the U3-overlapping. region of HIV nef inhibit HIV replication and infectivity in primary macrophages. (2006)
  • Author(s): Yamamoto T
  • Journal Title: Blood 108 Pages: 3305-3312
• [Journal Article] Involvement of TNF Receptor-associated Factor (TRAF) 6 in IL-25 Receptor Signaling (2006)
  • Author(s): Maezawa, Y.
  • Journal Title: J Immunol. 176 Pages: 1013-1018
• [Journal Article] Identification of DRG family regulatory proteins (DFRPs): specific regulation of DRG1 and DRG2. (2005)
  • Author(s): Ishikawa, K., Azuma, S., Ikawa, S., Semba, K, Inoue, J.
  • Journal Title: Genes Cells 10 Pages: 139-150
• [Journal Article] Interaction of antiproliferative protein Tob with poly(A)-bindig protein and inducible poly(A)-binding protein: Implication of Tob in translational control. (2005)
  • Author(s): Okochi, K., Suzuki, T., Inoue, J., Matsuda. S., Yamamoto, T.
  • Journal Title: Genes Cells 10 Pages: 151-163
• [Journal Article] Inhibitory activity of polyhydroxycarboxylate chelators against recombinant NF-κB p50 Protein-DNA binding. Bioorg. (2005)
  • Author(s): Sharma, R.K., Pande, V., Ramos, M.J., Rajor, H.K., Chopra, S., Meguro, K., Inoue, J., Otsuka, M.
  • Journal Title: Chem. 33 Pages: 67-81
• [Journal Article] RANK-mediated amplification of TRAF6 signaling leads to NFATc1 induction during osteoclastogenesis. (2005)
  • Author(s): Gohda, J., Akiyama, T., Koga, T., Takayanagi, H., Tanaka, S., Inoue, J.
  • Journal Title: EMBO J 24 Pages: 790-799
• [Journal Article] Dependence of Self-tolerance on TRAF6-directed Development of Thymic Stroma. (2005)
  • Author(s): Akiyama, T., Maeda, S., Yamane, S., Ogino, K., Kasai, M., Kajiura, F., Matsumoto, M., Inoue, J.
  • Journal Title: Science 308(5719) Pages: 248-251
• [Journal Article] Identification and characterization of Xenopus laevis homologs of mammalian TRAF6 and its binding protein TIFA. (2005)
  • Author(s): Inoue, J., Yagi, S., Ishikawa, K., Azuma, S., Ikawa, S., Semba, K.
  • Journal Title: Gene 358 Pages: 53-59
• [Journal Article] Recruitment of TRAF family proteins to The ASK1 signalosome is essential for oxidative stress-induced cell death. (2005)
  • Author(s): Noguchi, T., Takeda, K., Matsuzawa, A., Saegusa, K., Nakano, H., Gohda, J., Inoue, J., Ichijo, H.
  • Journal Title: J. Biol. Chem. 280(44) Pages: 37033-37040
• [Journal Article] Dependence of Self-tolerance on TRAF6-directed Development of Thymic Stroma (2005)
  • Author(s): Akiyama, T.
  • Journal Title: Science 308 Pages: 248-251
• [Journal Article] Identification and characterization of Xenopus laevis homologs of mammalian TRAF6 and its binding protein TIFA (2005)
  • Author(s): Inoue, J.
  • Journal Title: Gene 358 Pages: 53-59
• [Journal Article] Recruitment of TRAF family proteins to The ASK1 signalosome is essential for oxidative stress-induced cell death (2005)
  • Author(s): Noguchi, T.
  • Journal Title: J.Biol.Chem. 280 Pages: 37033-37040
• [Presentation] 膵臓がんにおいて Nuclear Factor-κB inducing kinase(NIK)はNF-kBの恒常的活性化と細胞増殖に寄与する (2009)
  • Author(s): 仁科隆史
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-02
• [Presentation] Basalタイプ乳癌細胞におけるNF-κB inducing kinase(NIK)発現亢進のメカニズム解析 (2009)
  • Author(s): 山本瑞生
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-01
• [Presentation] 乳癌における新規NF-κB標的遺伝子の探索 (2009)
  • Author(s): 伊藤拓
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-01
• [Presentation] Brm型SWI/SNF複合体とNF-κB新規経路におけるRelB/p52ダイマーを介在するREQUIEMの同定 (2009)
  • Author(s): 丹藤利夫
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-01
• [Presentation] Molecular mechanisms underlying enhanced expression of NF-kappaB inducing kinase(NIK)in basal type breast cancer cells. (2009)
  • Author(s): 山本瑞生、山口憲孝、仙波憲太郎、井上純一郎
  • Organizer: 第68回日本癌学会学術総会
• [Presentation] Screening of novel NF-kappaB target genes in breast cancer cells (2009)
  • Author(s): 伊藤拓、山口憲孝、仙波憲太郎、井上純一郎
  • Organizer: 第68回日本癌学会学術総会
• [Presentation] Requiem protein links RelB/p52 with Brm-tipe SWI/SNF in noncanonical NFkB pathway and is a therapeutic target of cancer (2009)
  • Author(s): 丹藤利夫、原口健、水谷壮利、秋山泰身、井上純一郎、伊庭英夫
  • Organizer: 第68回日本癌学会学術総会
• [Presentation] NIK is involved in constitutive activation of NF-kB and proliferation in pancreatic cancer cells (2009)
  • Author(s): 仁科隆史、山口憲孝、仙波憲太郎、井上純一郎
  • Organizer: 第68回日本癌学会学術総会
• [Presentation] 破骨細胞形成に必須な持続的RANKシグナルの伝達機構 (2008)
  • Author(s): 田口祐
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-12
• [Presentation] ATLにおける恒常的NFκB活性化機構の解析 (2008)
  • Author(s): 合田仁
  • 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: 2008-10-29
• [Presentation] NIK依存的なNFkappaB恒常的活性化は乳癌細胞の増殖を促進する (2008)
  • Author(s): 山口憲孝
  • 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: 2008-10-29
• [Presentation] 癌骨転移に関与するは骨細胞の新規分化機構の解明 (2008)
  • Author(s): 田口祐
  • 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] TAK1のK63型ポリユビキチン化は複合体形成を誘導することでTAK1自身の活性化を促し、NFκB活性化を制御する (2008)
  • Author(s): 山崎孔輔
  • 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] 癌骨転移に関与するは骨細胞の新規分化機構の解明 (2008)
  • Author(s): 田口祐、合田仁、井上純一郎
  • Organizer: 第67回日本癌学会学術総会
• [Presentation] TAK1のK63型ポリユビキチン化は複合体形成を誘導することでTAK1自身の活性化を促し、NFκB活性化を制御する (2008)
  • Author(s): 山崎孔輔、合田仁、金山敦宏、櫻井宏明、井上純一郎
  • Organizer: 第67回日本癌学会学術総会
• [Presentation] ATLにおける恒常的NFκB活性化機構の解析 (2008)
  • Author(s): 合田仁、柴田佑里、井上純一郎
  • Organizer: 第67回日本癌学会学術総会
• [Presentation] IK依存的なNFkappaB恒常的活性化は乳癌細胞の増殖を促進する (2008)
  • Author(s): 山口憲孝、仙波憲太郎、井上純一郎
  • Organizer: 第67回日本癌学会学術総会
• [Presentation] 非小細胞肺がん細胞株における変異EGFRのシグナルネットワーク解明 (2007)
  • Author(s): 仙波憲太郎
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-14
• [Presentation] 胸腺髄質上皮細胞の分化におけるRANKシグナルの役割 (2007)
  • Author(s): 秋山泰身
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-14
• [Presentation] SILACを用いたLPS活性化マクロファージにおけるチロシンリン酸化のタンパク質の同定 (2007)
  • Author(s): 松村隆之
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-14
• [Presentation] TRAFタンパク質によるNF-kB活性化機構とその生理機能 (2007)
  • Author(s): 井上純一郎
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-14
• [Presentation] TRAF6欠損によるTCR依存的なAP-1の活性化及び細胞増殖の亢進 (2007)
  • Author(s): 茂木秀彦
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-13
• [Presentation] アダプター分子としての機能を担う事でMEKK3はNFkB活性化を制御する (2007)
  • Author(s): 山崎孔輔
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-13
• [Presentation] Characterization of breast cancer cells with constitutively activated NFkappaB (2007)
  • Author(s): 山口憲孝
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-13
• [Presentation] ヒト母乳成分のヒトラクトフェリンはTLR4を介してNF-K B活性化を引き起こす (2007)
  • Author(s): 長谷川恵一
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-12
• [Presentation] 疾患メカニズムの解明に向けたチロシンリン酸化ネットワークに関する包括的動態解析 (2007)
  • Author(s): 尾山大明
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-12
• [Presentation] 破骨細胞形成におけるRANK依存的co-stimulatoryシグナルを継続的に誘導する分子機構 (2007)
  • Author(s): 田口祐
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-12
• [Presentation] チロシンリン酸化プロテオームに関する高速時系列解析システムの確立 (2007)
  • Author(s): 秦裕子
  • Organizer: 第30回日本分子生物学会年会 第80会日本生化学会大会 合同大会
  • Place of Presentation: パシフィコ横浜 横浜グランドインターコンチネンタルホテル
  • Year and Date: 2007-12-12
• [Presentation] Phospho-proteomics analysis of EGFR signal cascades in a non-small cell cancer cell line expressing mutated EGFR (2007)
  • Author(s): 宮坂隆
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-05
• [Presentation] Analysis of signal transduction pathways that cause constitutive activation of NF-kappaB in adult T cell leukemia cells (2007)
  • Author(s): 仁科隆史
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] Characterization of breast cancer cells with constitutively activated NFkB (2007)
  • Author(s): 山口憲孝
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] Bioinformatical estimation of EGFR signaling networks from quantitative phosphoproteome data (2007)
  • Author(s): 尾山大明
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] Cell-freeシステムを用いたHTLV-1 TaxによるNF-kB活性化機構の解明 (2007)
  • Author(s): 柴田佑里
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] Description of phosphotyrosine-dependent signaling network dynamics by quantitative proteomics (2007)
  • Author(s): 秦裕子
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-04
• [Presentation] 細胞シグナル伝達因子の制御による樹状細胞の人為的活性化 (2007)
  • Author(s): 秋山泰身
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-10-03
• [Presentation] TRAFシグナルによるNF-κB活性化機構とその生理機能 (2007)
  • Author(s): 井上純一郎
  • Organizer: 第28回日本炎症・再生医学会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2007-08-02
• [Presentation] Identification of TRAF6 as a critical intracellular signal transducer for controlling autoimmunity (2007)
  • Author(s): Jun-ichiro Inoue
  • Organizer: RCAI-JSI International Sympojium on Immunology 2007
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-07-26
• [Presentation] Human T cell leukemia virus type 1 (HTLV-1) Tax-mediated NF-kappaBactivation is independent of lys-63-linked type polyubiquitination (2007)
  • Author(s): 合田仁
  • Organizer: 第13回国際ヒトレトロウイルスHTLV会議
  • Place of Presentation: 箱根プリンスホテル
  • Year and Date: 2007-05-24
• [Presentation] 転写因子NF-κB活性化シグナルと免疫制御 (2007)
  • Author(s): 井上純一郎
  • Organizer: 第19回日本神経免疫学会学術集会
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2007-04-12
• [Presentation] 細胞シグナル伝達因子の制御による樹状細胞の人為的活性化, The design of a system to activate dendritic cells by modifying an intracellular signal transduction molecule (2007)
  • Author(s): 秋山泰身、秦俊文、下茂佑輔、大島大輔、井上純一郎
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] Analysis of signal transduction pathways that cause constitutive activation of NF-kappaB in adult T cell leukemia cells (2007)
  • Author(s): 仁科隆史、合田仁、井上純一郎
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] Characterization of breast cancer cells with constitutively activated NFkB (2007)
  • Author(s): 山口憲孝、仙波憲太郎、井上純一郎
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] Bioinformatical estimation of EGFR signaling networks from quantitative phosphoproteome data (2007)
  • Author(s): 尾山大明、秦裕子、菅野純夫、仙波憲太郎、井上純一郎、山本雅
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] Cell-freeシステムを用いたHTLV-1 TaxによるNF-kB活性化機構の解明, Establishment and characterization of the cell-free NF-kB activation system induced by recombinant Tax protein of HTLV-1 (2007)
  • Author(s): 柴田佑里、合田仁、井上純一郎
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] Description of phosphotyrosine-dependent signaling network dynamics by quantitative proteomics (2007)
  • Author(s): 秦裕子、尾山大明、菅野純夫、仙波憲太郎, 井上純一郎、山本雅
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] Phospho-proteomics analysis of EGFR signal cascades in a non-small cell cancer cell line expressing mutated EGFR (2007)
  • Author(s): 宮坂隆、秦裕子、尾山大明、菅野純夫、入江新司、佐藤孝明、井上純一郎、仙波憲太郎、山本雅
  • Organizer: 第66回日本癌学会学術総会
• [Presentation] 乳癌細胞におけるNotch3の遺伝子増幅による増殖促進作用 (2006)
  • Author(s): 山口憲孝、仙波憲太郎、合田仁、井上純一郎
  • Organizer: 第65回日本癌学会学術総会
• [Presentation] ATLにおける転写因子NFkB活性化機構の解析 (2006)
  • Author(s): 合田仁、仁科隆史、井上純一郎
  • Organizer: 第65回日本癌学会学術総会
• [Presentation] IL-1RシグナルにおけるTRAF6によるNFkB活性化機構 (2006)
  • Author(s): 山崎孔輔、合田仁、金山敦広、井上純一郎
  • Organizer: 第65回日本癌学会学術総会
• [Presentation] 乳癌における新規遺伝子増幅部位の同定 (2006)
  • Author(s): 仙波憲太郎、山口憲孝、清水健、砂川正勝、小山徹也、井上純一郎
  • Organizer: 第65回日本癌学会学術総会
• [Presentation] TRAF6依存性シグナル伝達の制御による癌免疫療法の基礎的検討 (2006)
  • Author(s): 秋山泰身、大島大輔、下茂佑輔、井上純一郎
  • Organizer: 第65回日本癌学会学術総会
• [Presentation] 乳癌細胞においてerbB2の過剰発現と相関する遺伝子群の同定 (2005)
  • Author(s): 仙波憲太郎、山口憲孝、井上純一郎
  • Organizer: 第64回日本癌学会学術総会
• [Presentation] ATLにおけるNFkB活性化機構の解析 (2005)
  • Author(s): 合田仁、入沢正人、井上純一郎
  • Organizer: 第64回日本癌学会学術総会
• [Presentation] 癌細胞における転写因子NFkBの恒常的活性化機構の解析 (2005)
  • Author(s): 山口憲孝、仙波憲太郎、合田仁、井上純一郎
  • Organizer: 第64回日本癌学会学術総会
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/BunshiHatsugan/index.html
• [Remarks]
  • URL: http://www.ims.u-tokyo.ac.jp/BunshiHatsugan/index.html