2001 年度実績報告書

遺伝子情報を機能情報に変換する試み

研究課題

研究課題/領域番号	11695085
研究機関	東京医科歯科大学
研究代表者	山村康子東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (50146809)
研究分担者	大谷清東京医科歯科大学, 疾患遺伝子実験センター, 講師 (30201974) 吉仲由之東京医科歯科大学, 疾患遺伝子実験センター, 助教授 (30024657) 中村正孝東京医科歯科大学, 疾患遺伝子実験センター, 教授 (30180392) 波呂浩孝東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (10313264)
キーワード	遺伝子情報 / 機能情報 / 近縁遺伝子群 / Smad / p51 / Tax / MMP
研究概要	ヒト疾病に関与する多くの疾患原因遺伝子についは機能解析が進み、疾患の表現型と原因遺伝子の生理機能との関連が明らかにされている。しかし、ゲノム解析や既知の遺伝子との相同性により単離、同定された新規遺伝子の生理機能は未だ不明なものが多い。そこで本研究においては、細胞におけるシグナル伝達や転写調節に関与する近縁遺伝子群の機能を比較、解析することにより、遺伝子情報から機能情報を予測する手法を確立しようと試みた。 1.TGF-βのシグナルを伝達するSmad転写因子群に属するSmad2とSmad3は構造的に高い相同性を有するが、細胞のG1期停止にはSmad2、Smad3が共に関与するが、アポトーシス誘導には主にSmad3が関与し、生理作用が異なることを明らかにした。 2.癌抑制遺伝子p53の類似遺伝子として同定されたp51遺伝子の遺伝子構造、生理機能をp53、p73遺伝子と比較することにより、p51遺伝子にはp53には見られない複数のアイソフォームが存在し、また、四肢、皮膚の分化における独自の機能を有することを見出した。 3.成人T細胞白血病ウイルス(HTLV-l)のTax遺伝子の変異とそのE2F転写因子活性化能を解析し、変異の構造的な意味を明らかにした。 4.軟骨分解活性を有するマトリックスメタロプロテアーゼ(MMP)群を構成するメンバーの生理機能、遺伝子構造を解析し、MMP-3遺伝子の活性化にはMMP-7刺激によりマクロファージから産生されるTNF-αが必須であることが見出された。

研究成果

(25件)

すべてその他

すべて文献書誌 (25件)

[文献書誌] Noriko Funato: "Common regulation of growth arrest and differentiation of osteoblasts by helix-loop-helix factors"Molecular and Cellular Biology. 21. 7416-7428 (2001)
[文献書誌] Ritsuko Iwanaga: "Molecular mechanism of cell cycle progression induced by the oncogene product Tax of HTLV-1"Oncogene. 20. 2055-2067 (2001)
[文献書誌] Yongping Huang: "Direct trans-activation of the uman cyclin D2 gene by the oncogene product Tax of HTLV-1"Oncogene. 20. 1094-1102 (2001)
[文献書誌] Yoshiaki Takahashi: "OX40 stimulation by gp34/OX40 ligand enhances productive HIV-1 infection"Journal of Virology. 75. 6748-6757 (2001)
[文献書誌] Kazuyuki Ogawa: "A novel serum protein that is selectively produced by cytotoxic lymphocytes"Journal of Immunology. 166. 6404-6412 (2001)
[文献書誌] Hiroyuki Hirai: "Prostaglandin d2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2"Journal of Experimental Medicine. 193. 255-261 (2001)
[文献書誌] Yasuko Yamamura: "Critical role of Smads and APO-1 complex in transforming growth factor-β-dependent apoptosis"Journal of Biological Chemistry. 275. 36295-36302 (2000)
[文献書誌] Tomoko Matsuzaki: "Induction of erythroid differentiation by inhibition Ras/ERK pathway in a Friend murine leukemia cell line"Oncogene. 19. 1500-1508 (2000)
[文献書誌] Iyoko Katoh: "p51A(Tap63γ), a p53 homolog, accumulates in response to DNA damage for cell regulation"Oncogene. 19. 3126-3130 (2000)
[文献書誌] Hisaaki Shinohara: "Fas drives cell cycle progression in glioma cells via extracellular signal-regulated kinase activation"Cance Research. 60. 1766-1772 (2000)
[文献書誌] Ritsuko Iwanaga: "Requirement of cell growth for gene expression induced by the lactose and tetracycline repressor-operator combination system in a human T cell line"Biochemical and Biophysical Research Communications. 276. 546-552 (2000)
[文献書誌] Kiyoshi Ohtani: "Cell type-specific E2F activation and cell cycle progression induced by the oncogene product Tax of HTLV-1"Journal of Biological Chemistry. 275. 11154-11163 (2000)
[文献書誌] Hirotaka Haro: "Matrix metalloproteinase-7 is required for tumor necrosis factor-α release from activated macrophages"Journal of Clinical investigation. 105. 143-150 (2000)
[文献書誌] Hirotaka Haro: "Chondrocyte matrix metalloproteinase-3 is required for the generation of a macrophage chemoattractant"Journal of Clinical Investigation. 105. 133-141 (2000)
[文献書誌] Shuntaro Ikawa: "p53 family genes : structural comparison, expression and mutation"Cell Death and Differentiation. 6. 1154-1161 (1999)
[文献書誌] Shuntaro Ikawa: "Human p53-p51 (p53-related) fusion protein : a potent BAX transactivator"Japanese Journal of Cancer Research. 90. 596-599 (1999)
[文献書誌] Yoshiyuki Yoshinaka: "Induction of manganese-superoxide dismutase in MRC-5 cells persistently infected with an Alphavirus, Sindbis"Biochemical and Biophysical Research Communications. 261. 139-143 (1999)
[文献書誌] Ken-ichi Aisaki: "Apoptotic changes precede mitochondrial dysfunction in red cell type pyruvate kinase mutant mouse erythroleukemia cell lines"Japanese Journal of Cancer Research. 90. 171-179 (1999)
[文献書誌] Masao Sunahara: "Mutational analysis of p51A/Tap63γ, a p53 homolog, in non-small cell lung cancer and breast cancer"Oncogene. 18. 3761-3765 (1999)
[文献書誌] Kinya Nagata: "Selective expression of a novel surface molecule by human Th2 cells in vivo"Journal of Immunology. 162. 1278-1286 (1999)
[文献書誌] Toshiaki Ohteki: "Interleukin 12-deopendent interferon γ production by CD8α^+ lymphoid dendric cells"Journal of Experimental Medicine. 189. 1981-1986 (1999)
[文献書誌] Tomonori Tsukahara: "Induction of Bcl-XL expression by HTLV-1 Tax through NF-κB in apoptosis-resistant T cell transfectants with Tax"Journal of Virology. 73. 7981-798 (1999)
[文献書誌] Youichi Iwanaga: "HTLV-1 Tax protein abrogates interleukin-2 dependence in a mouse T-cell line"Journal of Virology. 73. 1271-1277 (1999)
[文献書誌] Kiyoshi Ohtani: "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F"Oncogene. 18. 2299-2309 (1999)
[文献書誌] Hirotaka Haro: "Up-regulated expression of matrilysin and neutrophil collagenase in human herniated discs"Journal of Spinal Disorders. 12. 245-249 (1999)

2001 年度 実績報告書

遺伝子情報を機能情報に変換する試み

研究代表者

山村 康子 東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (50146809)

研究成果

[文献書誌] Noriko Funato: "Common regulation of growth arrest and differentiation of osteoblasts by helix-loop-helix factors"Molecular and Cellular Biology. 21. 7416-7428 (2001)

[文献書誌] Ritsuko Iwanaga: "Molecular mechanism of cell cycle progression induced by the oncogene product Tax of HTLV-1"Oncogene. 20. 2055-2067 (2001)

[文献書誌] Yongping Huang: "Direct trans-activation of the uman cyclin D2 gene by the oncogene product Tax of HTLV-1"Oncogene. 20. 1094-1102 (2001)

[文献書誌] Yoshiaki Takahashi: "OX40 stimulation by gp34/OX40 ligand enhances productive HIV-1 infection"Journal of Virology. 75. 6748-6757 (2001)

[文献書誌] Kazuyuki Ogawa: "A novel serum protein that is selectively produced by cytotoxic lymphocytes"Journal of Immunology. 166. 6404-6412 (2001)

[文献書誌] Hiroyuki Hirai: "Prostaglandin d2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2"Journal of Experimental Medicine. 193. 255-261 (2001)

[文献書誌] Yasuko Yamamura: "Critical role of Smads and APO-1 complex in transforming growth factor-β-dependent apoptosis"Journal of Biological Chemistry. 275. 36295-36302 (2000)

[文献書誌] Tomoko Matsuzaki: "Induction of erythroid differentiation by inhibition Ras/ERK pathway in a Friend murine leukemia cell line"Oncogene. 19. 1500-1508 (2000)

[文献書誌] Iyoko Katoh: "p51A(Tap63γ), a p53 homolog, accumulates in response to DNA damage for cell regulation"Oncogene. 19. 3126-3130 (2000)

[文献書誌] Hisaaki Shinohara: "Fas drives cell cycle progression in glioma cells via extracellular signal-regulated kinase activation"Cance Research. 60. 1766-1772 (2000)

[文献書誌] Ritsuko Iwanaga: "Requirement of cell growth for gene expression induced by the lactose and tetracycline repressor-operator combination system in a human T cell line"Biochemical and Biophysical Research Communications. 276. 546-552 (2000)

[文献書誌] Kiyoshi Ohtani: "Cell type-specific E2F activation and cell cycle progression induced by the oncogene product Tax of HTLV-1"Journal of Biological Chemistry. 275. 11154-11163 (2000)

[文献書誌] Hirotaka Haro: "Matrix metalloproteinase-7 is required for tumor necrosis factor-α release from activated macrophages"Journal of Clinical investigation. 105. 143-150 (2000)

[文献書誌] Hirotaka Haro: "Chondrocyte matrix metalloproteinase-3 is required for the generation of a macrophage chemoattractant"Journal of Clinical Investigation. 105. 133-141 (2000)

[文献書誌] Shuntaro Ikawa: "p53 family genes : structural comparison, expression and mutation"Cell Death and Differentiation. 6. 1154-1161 (1999)

[文献書誌] Shuntaro Ikawa: "Human p53-p51 (p53-related) fusion protein : a potent BAX transactivator"Japanese Journal of Cancer Research. 90. 596-599 (1999)

[文献書誌] Yoshiyuki Yoshinaka: "Induction of manganese-superoxide dismutase in MRC-5 cells persistently infected with an Alphavirus, Sindbis"Biochemical and Biophysical Research Communications. 261. 139-143 (1999)

[文献書誌] Ken-ichi Aisaki: "Apoptotic changes precede mitochondrial dysfunction in red cell type pyruvate kinase mutant mouse erythroleukemia cell lines"Japanese Journal of Cancer Research. 90. 171-179 (1999)

[文献書誌] Masao Sunahara: "Mutational analysis of p51A/Tap63γ, a p53 homolog, in non-small cell lung cancer and breast cancer"Oncogene. 18. 3761-3765 (1999)

[文献書誌] Kinya Nagata: "Selective expression of a novel surface molecule by human Th2 cells in vivo"Journal of Immunology. 162. 1278-1286 (1999)

[文献書誌] Toshiaki Ohteki: "Interleukin 12-deopendent interferon γ production by CD8α^+ lymphoid dendric cells"Journal of Experimental Medicine. 189. 1981-1986 (1999)

[文献書誌] Tomonori Tsukahara: "Induction of Bcl-XL expression by HTLV-1 Tax through NF-κB in apoptosis-resistant T cell transfectants with Tax"Journal of Virology. 73. 7981-798 (1999)

[文献書誌] Youichi Iwanaga: "HTLV-1 Tax protein abrogates interleukin-2 dependence in a mouse T-cell line"Journal of Virology. 73. 1271-1277 (1999)

[文献書誌] Kiyoshi Ohtani: "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F"Oncogene. 18. 2299-2309 (1999)

[文献書誌] Hirotaka Haro: "Up-regulated expression of matrilysin and neutrophil collagenase in human herniated discs"Journal of Spinal Disorders. 12. 245-249 (1999)

2001 年度実績報告書

山村康子東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (50146809)