2003 年度実績報告書

転写制御の異常と細胞の増殖・分化

研究課題

研究課題/領域番号	12215022
研究機関	東京大学
研究代表者	井上純一郎東京大学, 医科学研究所, 教授 (70176428)
キーワード	癌 / シグナル伝達 / 発現制御 / 骨形成 / 免疫 / 発生 / 器官形成
研究概要	本研究では、「転写因子の活性制御機構及び、転写因子の異常によって生じる細胞機能の破綻を分子レベルで解明する」ことを目的とする。特に我々が同定したシグナル伝達因子TRAF6によって活性化される転写因子NFκBとAP-1の制御機構及びその異常によって誘導される細胞増殖・分化の破綻に焦点を絞り、以下の結果を得た。1)昨年度同定したTRAF6活性化タンパク質TIFAの関連タンパク質TIFABを同定した。TIFABはTRAF6とは結合せずTIFAと結合し、TIFAによるNFκB活性化を抑制した。TIFABとTIFAの発現が同様の臓器特異性を示すことから両者が同一のシグナルにおいて正と負の制御を担っていると考えられた。2)CD40とRANKは同程度にNFκB, MAPKsを活性化し、その活性化はTRAF6に依存する。しかし、RANKは破骨細胞形成をTRAF6依存的に誘導するがCD40にはその活性は無い。その原因についてCD40/RANKキメラ受容体を用いて解析しRANKがTRAF6依存的にNFAT2を誘導するのに対してCD40では同程度のNFκB, MAPKs活性化が起こる条件でもNFAT2の誘導が起こらないことを示した。3)TRAF6のRING fingerのアミノ酸置換変異体(T6Rm)をTRAF6欠損細胞に発現させ検討した結果、in vivoにおいてもTRAF6がそのRING fingerを介してE3として機能しシグナルを伝達することが明らかとなった。

研究成果
(14件)

すべてその他

すべて文献書誌 (14件)

[文献書誌] Kittaka, A.: "Synthesis of oligonucleotides with 6-formyl-2'-O-methyluridine and thermal stability of their duplexes"Heterocycles. 59. 207-215 (2003)
[文献書誌] Gohda, J.: "Elimination of the vertabrate E.coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis"Oncogene. 22. 1340-1348 (2003)
[文献書誌] Takatsuna, H.: "Identification of TIFA as an adapter protein that links TRAF6 to IRAK-1 in IL-1 receptor signaling"J.Biol.Chem.. 278. 12144-12150 (2003)
[文献書誌] Matsumura, T.: "TRAF6-NF-κ B pathway is essential for IL-1-induced TLR2 expression and its functional response to TLR2 ligand in murine hepatocytes"Immunology. 109. 127-136 (2003)
[文献書誌] Ohsugi, M.: "Cdc2-mediated phosphorylation of chromokinesin Kid controls its distribution to spindle and chromosomes"EMBO J.. 22. 2091-2103 (2003)
[文献書誌] Matsuzawa-Watanabe, Y.: "Transcriptional activity of testis-determining factor SRY is modulated by the Wilms'tumor gene product, WT1"Oncogene. 22. 7900-7903 (2003)
[文献書誌] Tanaka, S.: "Signal transduction pathways regulating osteoclast differentiation and function"J Bone Miner.Metab.. 21. 123-133 (2003)
[文献書誌] Ishikawa, K.: "Cloning and characterization of Xenopus laevis drg2, a member of the developmentally regulated GTP-binding protein subfamily"Gene. 322. 105-112 (2003)
[文献書誌] Niu, Y.: "MIP-T3 associates with IL-13RK1 and suppresses STAT6 activation in response to IL-13 stimulation"FEBS Letter. 550. 139-143 (2003)
[文献書誌] Ito, E.: "A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1, is induced by the Ewing's sarcoma-Wilms'tumor 1 fusion protein of desmoplastic small round cell tumor"Am.J.Path.. 163. 2165-2172 (2003)
[文献書誌] Gohda, J.: "Down-regulation of TNF receptors by conophylline in human T-cell Leukemia cells"Int.J.Oncology. 23. 1373-1379 (2003)
[文献書誌] Luftig, M.: "Epstein-Barr virus latent membrane protein 1 activation of NF κ B through IRAK1 and TRAF6"Proc.Natl.Acad.Sci.USA. 100. 15595-15600 (2003)
[文献書誌] Ohazama, A.: "Traf6 is essential for murine tooth cusp morphogenesis"Development Dynamics. 229. 131-135 (2004)
[文献書誌] Matsumura, T.: "TGF β down-regulates IL-1 α -induced TLR2 expression in murine hepatocytes"J.Leukoc.Biol.. In press. (2004)

2003 年度 実績報告書

転写制御の異常と細胞の増殖・分化

研究代表者

井上 純一郎 東京大学, 医科学研究所, 教授 (70176428)

研究成果

[文献書誌] Kittaka, A.: "Synthesis of oligonucleotides with 6-formyl-2'-O-methyluridine and thermal stability of their duplexes"Heterocycles. 59. 207-215 (2003)

[文献書誌] Gohda, J.: "Elimination of the vertabrate E.coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis"Oncogene. 22. 1340-1348 (2003)

[文献書誌] Takatsuna, H.: "Identification of TIFA as an adapter protein that links TRAF6 to IRAK-1 in IL-1 receptor signaling"J.Biol.Chem.. 278. 12144-12150 (2003)

[文献書誌] Matsumura, T.: "TRAF6-NF-κ B pathway is essential for IL-1-induced TLR2 expression and its functional response to TLR2 ligand in murine hepatocytes"Immunology. 109. 127-136 (2003)

[文献書誌] Ohsugi, M.: "Cdc2-mediated phosphorylation of chromokinesin Kid controls its distribution to spindle and chromosomes"EMBO J.. 22. 2091-2103 (2003)

[文献書誌] Matsuzawa-Watanabe, Y.: "Transcriptional activity of testis-determining factor SRY is modulated by the Wilms'tumor gene product, WT1"Oncogene. 22. 7900-7903 (2003)

[文献書誌] Tanaka, S.: "Signal transduction pathways regulating osteoclast differentiation and function"J Bone Miner.Metab.. 21. 123-133 (2003)

[文献書誌] Ishikawa, K.: "Cloning and characterization of Xenopus laevis drg2, a member of the developmentally regulated GTP-binding protein subfamily"Gene. 322. 105-112 (2003)

[文献書誌] Niu, Y.: "MIP-T3 associates with IL-13RK1 and suppresses STAT6 activation in response to IL-13 stimulation"FEBS Letter. 550. 139-143 (2003)

[文献書誌] Ito, E.: "A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1, is induced by the Ewing's sarcoma-Wilms'tumor 1 fusion protein of desmoplastic small round cell tumor"Am.J.Path.. 163. 2165-2172 (2003)

[文献書誌] Gohda, J.: "Down-regulation of TNF receptors by conophylline in human T-cell Leukemia cells"Int.J.Oncology. 23. 1373-1379 (2003)

[文献書誌] Luftig, M.: "Epstein-Barr virus latent membrane protein 1 activation of NF κ B through IRAK1 and TRAF6"Proc.Natl.Acad.Sci.USA. 100. 15595-15600 (2003)

[文献書誌] Ohazama, A.: "Traf6 is essential for murine tooth cusp morphogenesis"Development Dynamics. 229. 131-135 (2004)

[文献書誌] Matsumura, T.: "TGF β down-regulates IL-1 α -induced TLR2 expression in murine hepatocytes"J.Leukoc.Biol.. In press. (2004)

2003 年度実績報告書

井上純一郎東京大学, 医科学研究所, 教授 (70176428)