1999 Fiscal Year Annual Research Report
Project/Area Number |
09470244
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Research Institution | Fukushima Medical University |
Principal Investigator |
竹之下 誠一 福島県立医科大学, 医学部, 教授 (10167489)
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Co-Investigator(Kenkyū-buntansha) |
宮園 浩平 癌研究会, 附属研究所・生化学部, 部長 (90209908)
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Keywords | TGF-β / Smad / 癌抑制遺伝子 / 増殖因子 / 遺伝子診断 |
Research Abstract |
1.long distance sequencer methodを駆使することによって、Smad6遺伝子の構造(exon-intron構造)を決定し、Genbankに登録した。Smad6遺伝子は4箇所のエクソンでコードされていた。 2.Smad6はTGF-b/アクチビンシグナルのアンタゴニストとして作用し、Smad2のリン酸化は抑制するがSmad3のリン酸化は抑制しない。Smad6はSmad1のリン酸化も抑制し、TGF-bやBMPのシグナルも抑制する。 3.Smad7遺伝子のゲノム構造を決定し、Genbankに登録した。Smad7遺伝子は4箇所のエクソンでコードされていた。 4.Smad6とSmad7アミノ酸が類似しているうえ、エクソン境界が完全に一致している。3'側の非翻訳領域においても、この両者はホモロジーが認められ、非常に近い遺伝子であった。 5.様々な癌組織において、全コード領域での変異の検索を進めているが、これまでに、polymorphismは確認されているが、Smad6とSmad7遺伝子の変異は同定されていない。
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Research Products
(15 results)
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[Publications] Yagi K, et al: "Alternatively spliced variant of Smad2 lacking exon 3. Comparison with wild-type Smad2 and Smad3."Journal of Biological Chemistry. 274(2). 703-709 (1999)
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[Publications] Kawate S, et al: "Mutation analysis of transforming growth factor beta type II receptor, Smad2,and Smad4 in hepatocellular carcinoma."International Journal of Oncology. 14(1). 127-131 (1999)
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[Publications] Manda R, et al: "Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display."Genomics. 61(1). 5-14 (1999)
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[Publications] Zhang GJ, et al: "Tamoxifen-induced apoptosis in breast cancer cells relates to down-regulation of bcl-2, but not bax and bcl-X(L), without alteration of p53 protein levels."Clinical Cancer Research. 5(10). 2971-2977 (1999)
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[Publications] Shitara Y, et al: "No mutations of the Smad2 gene in human sporadic gastric carcinomas."Japanese Journal of Clinical Oncology. 29(1). 3-7 (1999)
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[Publications] Hanai J, et al: "Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter."Journal of Biological Chemistry. 274(44). 31577-31582 (1999)
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[Publications] Fujii M, et al: "Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation."Molecular Biology of the Cell. 10(11). 3801-3813 (1999)
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[Publications] Nishihara A, et al: "E1A inhibits transforming growth factor-beta signaling through binding to Smad proteins."Journal of Biological Chemistry. 274(40). 28716-28723 (1999)
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[Publications] Miyazono K: "Signal transduction by bone morphogenetic protein receptors: functional roles of Smad proteins. [Review][39 refs]"Bone. 25(1). 91-93 (1999)
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[Publications] Nakao A, et al: "Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice."Journal of Clinical Investigation. 104(1). 5-11 (1999)
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[Publications] Lu SL, et al: "Two divergent signaling pathways for TGF-beta separated by a mutation of its type II receptor gene."Biochemical & Biophysical Research Communications. 259(2). 385-390 (1999)
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[Publications] Yamagishi T, et al: "Bone morphogenetic protein-2 acts synergistically with transforming growth factor-beta3 during endothelial-mesenchymal transformation in the developing chick heart."Journal of Cellular Physiology. 180(1). 35-45 (1999)
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[Publications] Das P, et al: "Drosophila dSmad2 and Atr-I transmit activin/TGFbeta signals."Genes to Cells. 4(2). 123-134 (1999)
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[Publications] Kawabata M, et al: "Signal transduction of the TGF-beta superfamily by Smad proteins.[Review][67 refs]"Journal of Biochemistry. 125(1). 9-16 (1999)
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[Publications] Yanagisawa J, et al: "Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators."Science. 283(5406). 1317-1321 (1999)