MAD関連遺伝子の構造決定と機能解析

2000 年度 研究成果報告書概要

• 研究課題/領域番号: 09470244
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 外科学一般
• 研究機関: 福島県立医科大学 (1999-2000); 群馬大学 (1997-1998)
• 研究代表者: 竹之下 誠一 福島県立医科大学, 医学部, 教授 (10167489)
• 研究分担者: 志村 龍男 群馬大学, 医学部, 助手 (00282393) ; 浅尾 高行 群馬大学, 医学部, 助教授 (40212469) ; 宮園 浩平 東京大学, 大学院・医学系研究科, 教授 (90209908)
• 研究期間 (年度): 1997 – 2000
• キーワード: TGF-β / Smad / 癌抑制遺伝子 / 増殖因子 / 遺伝子診断

研究概要

対象遺伝子のヒトゲノム上の構造は、癌の臨床で行われるDNAを基質とした癌関連遺伝子の研究には不可欠なものである。我々は平成9年より、MAD関連遺伝子の構造決定と機能解析という研究課題の基に、TGF-βシグナル伝達系と癌との関連を明らかにするために、TGF-βシグナル伝達因子のなかのTGF-βII型受容体,Smad2 Smad3,Smad6,Smad7の遺伝子構造を決定し、様々な癌組織でのそれぞれの遺伝子異常の検討を行い報告してきた。今年度は、本プロジェクトの総括をした。
1.これまでにEMBL/GenBanKに登録した(Data Libraries under Accession Nos.)のは、
Smad2:U78726 to U78733
Smad3:AF025293 to AF025300,AB004922 to AB004930
Smad4(promotor):U44378
Smad6:AF041062 to AF041065
Smad7:AF026556 to AF026559
2.今回解析したTGF-βシグナル伝達因子のうちヒトの癌組織で遺伝子変異を確認できたのはSmad4、Smad2、TGF-βII型とI型受容体だけで、Smad3、Smad6、Smad7での異常は無かった。

研究成果

• [文献書誌] Nakao A, et al.: "TGF-β receptor-mediated signalling through Smad2, Smad3 and Smad4"EMBO J. 16(17). 5353-5362 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Heldin CH et al.: "TGF-β signalling from cell membrane to nucleus through SMAD proteins"Nature. 390(4). 465-471 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Imamura T, et al.: "Smad6 inhibits signalling by the TGF-β superfamily"Nature. 389(9). 622-626 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Transforming growth factor-β signaling pathway and its disruption in human cancer."Ann.Cancer Res.Ther.. 6:. 33-37 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Absence of mutations in the transforming growth factor-beta type II receptor in sporadic lung cancers with microsatellite instability and rare H-ras1 alleles."Carcinogenesis. 18:. 1427-1429 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and intron primers"Oncogene. 14. 1255-1258 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 竹之下誠一 他: "TGF-βレセプターとSmad"実験医学. 15(16). 137-142 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 竹之下誠一 他: "TGF-βの機能と病態への関与"G.I.Research. 5(5). 69-75 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 竹之下誠一 他: "TGF-βスーパーファミリー受容体"生体の科学. 48(5). 502-506 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 竹之下誠一: "TGF-βレセプターと癌抑制機構"実験医学. 15(9). 152-157 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Absence of mutations in the analysis of coding sequences of the entire transforming growth factor-beta type II receptor gene in sporadic human breast cancers."Oncol.Rep.. 5(2). 367-371 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Absence of mutation in the analysis of coding sequences of the entire transforming growth factor-beta type II receptor gene in sporadic human gastric cancer using genomic DNA and intron primers."Oncol.Rep.. 5(1). 77-80 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway."Genomics. 15;48(1). 1-11 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Tani M, et al.: "Genomic structure and chromosomal localization of the mouse Ogg1 gene that is involved in the repair of 8-hydroxyguanine in DNA damage."Mamm Genome. 9(1). 32-37 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nakajima Y, et al.: "Immunolocalization of latent transforming growth factor- β binding protein-1 (LTBP1) during mouse development : possible roles in epithelial and messenchymal cytodifferentitation."Cell Tissue Res.. 295. 257-267 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Guo RJ, et al.: "Analysis of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer."Carcinogenesis. 19(9). 1539-1544 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takenoshita S, et al.: "Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers."Carcinogenesis. 19(5). 803-807 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Shitara Y, et al.: "Mutation of the transforming growth factor-beta type II receptor gene is a rare event in human sporadic gastric carcinomas."Int.J.Oncol.. 12(5). 1061-1065 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yasumi K, et al.: "Transforming growth factor beta type II receptor (TGF beta R II) mutation in gastric lymphoma without mutator phenotype."Pathol.Int.. 48(2). 134-137 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Horie K, et al.: "Lack of transforming growth factor-beta type II receptor expression in human retinoblastoma cells."J.Cell Physiol.. 175(3). 305-313 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nishihara A, et al.: "Role of p300, a transcriptional coactivator, in signalling of TGF-beta."Genes Cells. 3(9). 613-623 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Li J, et al.: "Smad2 over expression enhances Smad4 gene expression and suppresses CBFA1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells."J.Biol.Chem.. 20;273(47). 31009-31015 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Goto D, et al.: "A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3, and has a dominant negative effect on TGF-beta signals."FEBS Lett.. 3;430(3). 201-204 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kawabata M, et al.: "Smad proteins exist as monomers in vivo and undergo homo and hetero-oligomerization upon activation by serine/threonine kinase receptors."EMBO J.. 15;17(14). 4056-4065 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Takeda K, et al.: "Identification of a novel bone morphogenetic protein-responsive gene that may function as a noncoding RNA."J.Biol.Chem.. 3;273(27). 17079-17085 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Shimizu A, et al.: "Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line."Genes Cells. 3(2). 125-134 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Lu SL, et al.: "HNPCC associated with germline mutation in the TGF-beta type II receptor gene."Nat.Genet.. 19(1). 17-18 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Manda R, et al: "Identification of genes (SPON2 and C20 or f2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display."Genomics. 61(1). 5-14 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Miyazono K: "Signal transduction by bone morphogenetic protein receptors : functional roles of Smad proteins. [Review][39 refs]"Bone. 25(1). 91-93 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yamagishi T, et al: "Bone morphogenetic protein-2 acts synergistically with transforming growth factor-beta 3 during endothelial-mesenchymal transformation in the developing chick heart."Journal of Cellular Physiology. 180(1). 35-45 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Das P, et al: "Drosophila d Smad2 and Atr-I transmit activin/TGF beta signals."Genes to Cells. 4(2). 123-134 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Miyazono K.: "Positive and negative regulation of TGF-beta signaling."J.Cell Sci.. 113(pt7). 1101-1109Review (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ishida W, et al: "Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter."Journal of Biological Chemistry. 275(9). 6075-6079 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kusanagi K, et al: "Characterization of a bone morphogenetic protein-responsive Smad-binding element."Mol.Biol.Cell.. 11(2). 555-565 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kawabata M, et al: "Intracellular signaling of the TGF-beta superfamily by Smad proteins."Ann.NY.Acad.Sci.. 886. 73-82Review (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] ten Dijke P, et al: "Signaling inputs converge on nuclear effectors in TGF-beta signaling."Trends Biochem.Sci.. 25(2). 64-70Review (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Tada K, et al: "Region between alpha-helices 3 and 4 of the mad homology 2 domain of Smad4 : functional roles in oligomer formation and transcriptional activation."Genes Cells.. 4(12). 731-741 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Miura S, et al: "Hgs (Hrs), a FYVE domain protein, is involved in smad signaling through cooperation with SARA."Molecular Cell Biology. 20(24). 9346-9355 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Miyazono K.: "TGF-beta/SMAD signaling and its involvement in tumor progression."Biol.Pharm.Bull.. 23(10). 1125-1130 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Zhang YW, et al: "A RUNX2/PEBP2 alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia."Proc.Natl.Acad.Sci.USA.. 97(19). 10549-10554 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Udagawa Y, et al: "Schnurri interacts with Mad in a Dpp-dependent manner."Genes Cells. 5(5). 359-369 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Miyazono K, et al: "TGF-beta signaling by Smad proteins."Adv.Immunol.. 75. 115-157 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Miyazono K.: "TGF-beta signaling by Smad proteins."Cytokine Growth Factor Rev.. 11(1-2). 15-22Review (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Wang D, et al: "Mutation analysis of the smad6 and smad7 gene in human ovarian cancers."International Journal of Oncology. 17(6). 1087-1091 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Osawa H, et al: "Mutation analysis of transforming growth factor beta type II receptor, smad2, smad3 and smad4 in esophageal squamous cell carcinoma."International Journal of Oncology. 17(4). 723-728 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Wang D, et al: "Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer."Cancer Reseach. 60(16). 4507-4512 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yoshida Y, et al: "Negative Regulation of BMP/Smad Signaling by Tob in Osteoblasts."Cell. 103(7). 1085-1097 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nishimori S, et al: "Smad-mediated transcription is required for TGF-beta 1-induced p57 Kip2 proteolysis in osteoblastic cells."Journal of Biological Chemistry. (epub ahead of print). (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kanai H, et al: "Transforming growth factor-ss/Smads signaling induces transcription of the cell type-restricted ankyrin repeat protein CARP gene through CAGA motif in vascular smooth muscle cells."Circ.Reseach. 88(1). 30-36 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Nakao A, et al.: "TGF-β receptor-mediated signaling through Smad2, Smad3 and Smad4."EMBO J.. 16(17). 5353-5362 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Heldin CH, et al.: "TGF-β signaling from cell membrane to nucleus through SMAD proteins."Nature. 390(4). 465-471 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Imamura T, et al.: "Smad6 inhibits signaling by the TGF-β superfamily."Nature. 389(9). 622-626 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Transforming growth factor-β signaling pathway and its disruption in human cancer."Ann.Cancer Res.Ther.. 6. 33-37 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Absence of mutations in the transforming growth factor-beta type II receptor in sporadic lung cancers with microsatellite instability and rare H-ras1 alleles."Carcinogenesis. 18. 1427-1429 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and intron primers."Oncogene. 14. 1255-1258 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Absence of mutations in the analysis of coding sequences of the entire transforming growth factor-beta type II receptor gene in sporadic human breast cancers."Oncol.Rep.. 5(2). 367-371 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Absence of mutation in the analysis of coding sequences of the entire transforming growth factor-beta type II receptor gene in sporadic human gastric cancer using genomic DNA and intron primers."Oncol.Rep.. 5(1). 77-80 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway."Genomics. 15 ; 48(1). 1-11 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tani M, et al.: "Genomic structure and chromosomal localization of the mouse Ogg1 gene that is involved in the repair of 8-hydroxyguanine in DNA damage."Mamm Genome. 9(1). 32-37 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Guo RJ, et al.: "Analysis of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer."Carcinogenesis. 19(9). 1539-1544 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Takenoshita S, et al.: "Mutation analysis of the Smad2 gene in human colon cancers using genomic DNA and intron primers."Carcinogenesis. 19(5). 803-807 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Shitara Y, et al.: "Mutation of the transforming growth factor-beta type II receptor gene is a rare event in human sporadic gastric carcinomas."Int.J.Oncol.. 12(5). 1061-1065 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yasumi K, et al.: "Transforming growth factor beta type II receptor (TGF beta R II) mutation in gastric lymphoma without mutator phenotype."Pathol.Int.. 48(2). 134-137 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Horie K, et al.: "Lack of transforming growth factor-beta type II receptor expression in human retinoblastoma cells."J.Cell Physiol.. 175(3). 305-313 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Nishihara A, et al.: "Role of p300, a transcriptional coactivator, in signalling of TGF-beta."Genes Cells. 3(9). 613-623 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Li J, et al.: "Smad2 over expression enhances Smad4 gene expression and suppresses CBFA1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells."J.Biol.Chem.. 20 ; 273(47). 31009-31015 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Goto D, et al.: "A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3, and has a dominant negative effect on TGF-beta signals."FEBS Lett.. 3 ; 430(3). 201-204 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kawabata M, et al.: "Smad proteins exist as monomers in vivo and undergo homo and hetero-oligomerization upon activation by serine/threonine kinase receptors."EMBO J.. 15 ; 17(14). 4056-4065 (1998)
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• [文献書誌] Takeda K, et al.: "Identification of a novel bone morphogenetic protein-responsive gene that may function as a noncoding RNA."J.Biol.Chem.. 3 ; 273(27). 17079-17085 (1998)
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• [文献書誌] Shimizu A, et al.: "Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line."Genes Cells. 3(2). 125-134 (1998)
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• [文献書誌] Lu SL, et al.: "HNPCC associated with germline mutation in the TGF-beta type II receptor gene."Nat Genet. 19(1). 17-18 (1998)
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• [文献書誌] 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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• [文献書誌] Nakajima Y, et al.: "Immunolocalization of latent transforming growth factor-β binding protein-1 (LTBP1) during mouse development : possible roles in epithelial and messenchymal cytodifferentitation."Cell Tissue Res.. 295. 257-267 (1999)
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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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. 50(10). 2971-2977 (1999)
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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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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• [文献書誌] 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)
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• [文献書誌] Kawabata M, et al.: "Intracellular signaling of the TGF-beta superfamily by Smad proteins."Ann.NY.Acad.Sci.(Review). 886. 73-82 (1999)
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• [文献書誌] Tada K, et al.: "Region between alpha-helices 3 and 4 of the mad homology 2 domain of Smad4 : functional roles in oligomer formation and transcriptional activation."Genes Cells. 4(12). 731-741 (1999)
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• [文献書誌] Miyazono K.: "Positive and negative regulation of TGF-beta signaling."J.Cell Sci.(Review). 113(pt7). 1101-1109 (2000)
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• [文献書誌] Ishida W, et al.: "Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter."Journal of Biological Chemistry. 275(9). 6075-6079 (2000)
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• [文献書誌] Kusanagi K, et al.: "Characterization of a bone morphogenetic protein-responsive Smad-binding element."Mol.Biol.Cell.. 11(2). 555-565 (2000)
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• [文献書誌] ten Dijke P, et al.: "Signaling inputs converge on nuclear effectors in TGF-beta signaling."Trends Biochem.Sci.(Review). 25(2). 64-70 (2000)
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• [文献書誌] Miura S, et al.: "Hgs (Hrs), a FYVE domain protein, is involved in smad signaling through cooperation with SARA."Molecular Cell Biology. 20(24). 9346-9355 (2000)
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• [文献書誌] Miyazono K.: "TGF-beta/SMAD signaling and its involvement in tumor progression."Biol.Pharm.Bull.. 23(10). 1125-1130 (2000)
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• [文献書誌] Zhang YW, et al.: "A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and smad interaction in cleidocranial dysplasia."Proc.Natl.Acad.Sci.USA.. 97(19). 10549-10554 (2000)
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• [文献書誌] Udagawa Y, et al.: "Schnurri interacts with Mad in a Dpp-dependent manner."Genes Cells. 5(5). 359-369 (2000)
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• [文献書誌] Miyazono K, et al.: "TGF-beta signaling by Smad proteins."Adv.Immunol.. 75. 115-157 (2000)
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• [文献書誌] Miyazono K, et al.: "TGF-beta signaling by Smad proteins."Cytokine Growth Factor Rev.(Review). 11(1-2). 15-22 (2000)
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• [文献書誌] Wang D, et al.: "Mutation analysis of the smad6 and smad7 gene in human ovarian cancers."International Journal of Oncology. 17(6). 1087-1091 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Osawa H, et al.: "Mutation analysis of transforming growth factor beta type II receptor, smad2, smad3 and smad4 in esophageal cell carcinoma."International Journal of Oncology. 17(4). 723-728 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Wang D, et al.: "Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer."Cancer Research. 60(16). 4507-4512 (2000)
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• [文献書誌] Yoshida Y, et al.: "Negative Regulation of BMP/Smad Signaling by Tob in Osteoblasts."Cell. 103(7). 1085-1097 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Nishimori S, et al.: "Smad-mediated transcription is required for TGF-beta 1-induced p57Kip2 proteolysis in osteoblastic cells."Journal of Biological Chemistry. (equb ahead of print). (2001)
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• [文献書誌] Kanai H, et al.: "Transforming growth factor-ss/Smads signaling induces transcription of the cell type-restricted ankyrin repeat protein CARP gene through CAGA motif in vascular smooth muscle cells."Circ.Research. 88(1). 30-36 (2001)
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