TGF-β-DPC-4 mediated cell cycle regulation

• Project/Area Number: 09470042
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo (1998); Osaka University (1997)
• Principal Investigator: AKIYAMA Tetsu Institute of Molecular and Cellular Biosciences, The University of Tokyo, 分子細胞生物学研究所, 教授 (70150745)
• Co-Investigator(Kenkyū-buntansha): 石館 宇夫 東京大学分子細胞生物学研究所, 助手
• Project Period (FY): 1997 – 1998
• Project Status: Completed (Fiscal Year 1998)
• Budget Amount: ¥13,200,000 (Direct Cost: ¥13,200,000); Fiscal Year 1998: ¥4,900,000 (Direct Cost: ¥4,900,000); Fiscal Year 1997: ¥8,300,000 (Direct Cost: ¥8,300,000)
• Keywords: DPC4 / TGF-β / Target gene / One-hybrid / Subtraction / Cell Cycle / DPC-4, / TGF-b, / TAK1, / TAB-1, / 増殖制御、 / 細胞周期、 / シグナル伝達、 / 転写制御

Research Abstract

DPC4 (SMAD4) forms a complex with SMAD 2 /SMAD3, and induces transcriptional activation of TGF-beta target genes. We attempted to isolate target genes by yeast one-hybrid system using DPC4 as bait. We screened 2 x 105 clones of a human genome library and isolated three fragments that contain the consensus sequence recognized by DPC4. We searched for the DDBJ, EMBL and GenBank databases and found that one clone is a fragment of the human 28S rRNA gene. We are also trying to isolate DPC4 target genes involved in the regulation of cell cycle progression and signal transduction by the subtraction method and the promoter trap method. To understand the mechanism underlying the DPC4-mediated cell cycle regulation, we are also trying to identify novel DPC4-associated proteins.

Research Products

• [Publications] T.Nakamura et al.: "Axin,an inhibitor of the Wnt signaling pathway,interacts with β-catenin,GSK-3βand APC and reduces the β-catenin level"Genes Cells. 3. 395-403 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Senda et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system"Neuroscience. 83. 857-866 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Inoue et al.: "Wilms'tumor gene(WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells"Blood. 91. 2969-2976 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] H.Nakagawa et al.: "Identification of a brain-specific APC homologue,APCL,and its interaction with β-catenin"Cancer Res. 58. 5176-5181 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Y.Dabashi et al.: "CDK4,a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells"Biocyam.Biophys.Res.Commun. 253. 609-613 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Yamagami et al.: "Suppression of Wilms' tumor gene(WT1)expression in duces G2/M arrest in leukemic cells"Leuk.Res. 22. 383-384 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Mori et al.: "Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines"J.Hum.Genet. 43. 123-127 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Yamochi et al.: "Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by downregulation of BCL-2 and BCL-XL"Oncogene. 18. 487-494 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Tezuka et al.: "PSD-95 promoters Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A"Proc.Nathl.Acad.Sci. USA96. 435-440 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] F.Hamada et al.: "Negative regulation of Wingless signaling by D-Axin,a Drosophila homologue of Axin"Science. 283. 1739-1742
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Senda et al.: "Association of the MCC(Mutated in colorectal cancer)gene product to the plasma membrane and membrane organelles"Medical Electron Microscopy. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.Takemura et al.: "Nucleolar protein B23,1 binds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity"J.Biochem. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] R.B.Chandra et al.: "Localization of the GAP family SPAL in the Rat Esophagus and Heart"Medical Electronmicroscopy. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Nakamura et al.: "Axin, an inhibitor of the Wnt signaling pathway, interacts with β-catenin, GSK-3b and APC and reduces the β-catenin level."Genes Cells. 3. 395-403 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Senda et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system."Neuroscience. 83. 857-866 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K. Inoue et al.: "Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells."Blood. 91. 2969-2976 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] H. Nakagawa et al.: "Identification of a brain-specific APC homologue, APCL, and its interaction with β-catenin."Cancer Res.. 58. 5176-5181 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Y. Dobashi et al.: "CDK4, a possible critical regulator of apotosis in rat pheochromocytoma PC12 cells."Biochem. Biophys. Res. Commun.. 253. 609-613 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Yamagami et al.: "Suppression of Wilm's tumor gene (WT1) ezpression induces G2/M arrest in leukemic cells."Leuk. Res.. 22. 383-384 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K. Mori et al.: "Identification of brain-specificsplicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines."J. Hum. Genet.. 43. 123-127 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Yamochi et al.: "Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accopanied by downregulation of BCL-2 and BCL-XL."Oncogene. 18. 487-494 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Tezuka et al.: "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methy1-D-aspartatereceptor submit NR2A."Proc, Natl. Acad. Sci. USA96. 435-440 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] F. Hamada et al.: "Negative regulation of Wingless signaling by D-Axin, a Drosphila homologue of Axin."Science. 283. 1739-1742 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T. Senda et al.: "Association of the MCC (Mutated in colorectal cancer) gene product to the plasma membrane and membrane organelles."Medical Electron Microscopy. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Tkemura et al.: "Nucleolar protein B23.1 nbinds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity."J. Bilohem. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] R. B. Chandra et al.: "Localization of the GAP family SPAL in the Rat Esophagus and Heart."Medical Electronmicroscopy. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] T.Nakamura et al.: "Axin,an inhibitor of the Wnt signaling pathway,interacts with β-catenin,CSK-3β and APC and reduces the β-catenin level." Genes Cells. 3. 395-403 (1998)
• [Publications] T.Senda et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system." Neuroscience. 83. 857-866 (1998)
• [Publications] K.Inoue et al.: "Wilms'tumor gene(WT1)competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)
• [Publications] H.Nakagawa et al.: "Identification of a brain-specific APC homologue,APCL,and its interaction with β-catenin." Cancer Res.58. 5176-5181 (1998)
• [Publications] Y.Dabashi et al.: "CDK4,a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells." Biochem.Biophys.Res.Commun.253. 609-613 (1998)
• [Publications] T.Yamagami et al.: "Suppression of Wilms'tumor gene(WT1)expression induces G2/M arrest in leukemic cells." Leuk.Res.22. 383-384 (1998)
• [Publications] K.Mori et al.: "Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines." J.Hum.Genet.43. 123-127 (1998)
• [Publications] T.Yamochi et al.: "Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by downregulation of BCL-2 and BCL-XL." Oncogene. 18. 487-494 (1999)
• [Publications] T.Tezuka et al.: "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A." Proc.Natl.Acad.Sci.USA96. 435-440 (1999)
• [Publications] F.Hamada et al.: "Negative regulation of Wingless signaling by D-Axin,a Drosophila homologue of Axin." Science. 283. 1739-1742
• [Publications] T.Senda et al.: "Association of the MCC(Mutated in colorectal cancer)gene product to the plasma membrane and membrane organelles." Medical Electron Microscopy. (in press).
• [Publications] M.Takemura et al.: "Nucleolar protein B23.1 binds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity." J.Biochem.(in press).
• [Publications] R.B.Chandra et al.: "Localization of the GAP family SPAL in the Rat Esophagus and Heart." Medical Electronmicroscopy. (in press).
• [Publications] K.Satoh et al.: "DAP-1,a novel proteinthat interacts with the guanylate kinase-like domains of DLG and PSD-95." Genes to Cells. 2. 415-424 (1997)
• [Publications] T.Ishidate et al.: "Identification of a novel nuclear localization signal in Sam68." FEBS LETTERS. 409. 237-241 (1997)
• [Publications] M.Moriyama et al.: "The BCL-6 protein is phosphorylated at multiple sites in its serine-and proline-clustered region by mitogen activated protein kinase(MAPK)in vivo." Oncogene. 14. 2465-2474 (1997)
• [Publications] T,Kiyono et al.: "Binding of high risk HPV E6 oncoproteins to PDZ-domain-containing proteins." Proc. Natl. Acad. Sci. USA. 94. 11616-11612 (1997)
• [Publications] Y.Murata et al.: "The Wilms tumor suppressor gene WT1 induces G1 arrest and apoptosis in myeloblastic leukemia M1 cells." FEBS LLETTERS.409. 41-45 (1997)
• [Publications] H.Shibata et al.: "Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene." Science. 278. 120-123 (1997)
• [Publications] T.Senda et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system." Neuroscience. 83. 857-866 (1998)
• [Publications] T.Yamagami et al.: "Suppression of Wilms tumor gene(WT1)expression induces G2/M arest in leukemic cells." Leukemia Res.(in press).
• [Publications] T.Senda et al.: "Association of the MCC(Multated in colorectal cancer)gene product to the plasma membrane and membrane organelles." Medical Electron Microscopy. (in press).
• [Publications] K.Inoue et al.: "Wilms tumor gene(WT1) competes with differentiation-induced signal in hematopoietic progenitor cells." Blood. (in press).
• [Publications] M.Takemura et al.: "Phosphorylated retinoblastoma protein stimulates DNA polymerase" Oncogene. 15. 2483-2492 (1997)
• [Publications] Y.Dobashi et al.: "The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle." Mol. Cell. Biochem.171. 121-126 (1997)
• [Publications] I.Miyashiro et al.: "Midkine expression in human breast cancers: Expression of truncated form." Breast Can. Res. Treatment. 43. 1-6 (1997)
• [Publications] K.Kagawa et al.: "Overexpression of GML promotes radiation-induced cell cycle arrest and apoptosis." Biochem. Biophys. Res. Commun.241. 481-485 (1997)
• [Publications] Y.Dobashi et al.: "Cell cycle control with minimal participation of CDK2 in a murine fibrosarcoma clone cultured in protein-free medium." Biochem. Biophys. Res. Commun.232. 622-625 (1997)
• [Publications] J.Adachi et al.: "Growth suppression of non-small cell lung carcinoma cells by the introduction of the p16INK4A gene." Int. J. Cancer. 10. 33-39 (1997)