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Implication of transcriptional coactivator complexes in rheumatoid synovial cells

Research Project

Project/Area Number 12557045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 内科学一般
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

NAKAJIMA Toshihiro  St. Marianna University School of Medicine, Associate Professor, 難病治療研究センター, 助教授 (90260752)

Co-Investigator(Kenkyū-buntansha) AONO Hiroyuki  Santen Pharmaceutical CO., LTD,Team Reader, 研究開発部リウマチグループ, チームリーダー
FUKAMIZU Akiyoshi  Tsukuba University, Professor, 応用生物化学系, 教授 (60199172)
NISHIOKA Kusuki  St. Marianna University School of Medicine, Professor, 難病治療研究センター, 教授 (60049070)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2002: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywordstranscriptional coactivator / rheumatoid arthritis / CREB binding protein (CBP) / synovial cell / Notch 1 / yeast 2 hybrid screening / acetylation / tumor necrosis factor (TNF)-α / 細胞周期 / CREB結合蛋白質 / CREB結合タンパク質(CBP) / Notch-1 / 腫瘍壊死因子(TNF-α) / presenilin / 抑制剤 / 慢性関節リウマチ / 転写コアチクベーター / yeast 2-hybrid法 / NF-κB
Research Abstract

To assess the implication of transcriptional coactivator in rheumatoid synoviocytes activation, we attempted the following two approaches. One is evaluation of nuclear acetylation, one of the critical roles as coactivator function of CREB binding protein (CBP). The other is molecular cloning of CBP-interaction proteins in rheumatoid synoviocytes by yeast two-hybrid systems.
1) Using a specific antibody against acetylated lysine, we detected potent nuclear acetylation in rheumatoid synoviocytes and revealed that p53 is one of characteristically acetylated proteins. We further found that TNFα induced acetylation of p53 but attenuated its transcriptional activation in synoviocytes. As overexpression of CBP resulted in p53 promoter activation by TNFα, CBP recruitment is required for p53 activation.
2) We cloned Notch-1 as one of CBP-binding proteins from cDNA library prepared from rheumatoid synoviocytes. Notch-1 signal was characteristically activated in rheumatoid synoviocytes though TNFα signaling and implicated in synoviocytes proliferation by TNFα.
These results clearly suggested that coactivator takes crucial roles for rheumatoid synoviocytes activation and might contribute to clarifying the pathogenesis of RA.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (68 results)

All Other

All Publications (68 results)

  • [Publications] M.Nakazawa: "Role of Notch-1 intracellular domain in activation of rheumatoid Synoviocytes"Arthritis & Rheum. 44. 1545-1554 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Nakazawa: "NFkB2 (p52)promoter pathway in rheumatoid synoviocytes"International Journal of Molecular Medicine. 10. 269-275 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakazawa M: "NF□B2 (p52 ) promoter activation via Notch signaling pathway in rheumatoid synoviocytes"International Journal of Molecular Medicine. 7. 31-35 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakazawa M: "CBP : a target molecule of HTLV-1 Tax in synoviocyte activation"Biochem. Biophys. Res. Comm.. 269. 584-590 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Ishii: "Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients"Rheumatology International. 21. 10-14 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Taniguchi: "High Mobility Group Box Chromosomal Protein 1 Plays a Role in the Pathogenesis of Rheumatoid Arthritis as a Novel Cytokine"Arthritis and Rheumatism. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Hirose: "Regulation of CREB-mediated transcription by association of CDK4 binding protein p34 SEI-1 with CBP"International Journal of Molecular Medicine. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation"Arthritis & Rheum. 44. 1013-1021 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nguyen Ngoc Chau: "Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis patients"International Journal of Molecular Medicine. 10. 41-48 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Ohshima: "Effects of interaction between parvovirus minute virus of mice NS1 and p53-transactivation"International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] KP.Sarker: "Inhibition of Caspase-3 Activation by SB203580, p38 Mitogen-Activated ProteinKinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells"Journal of Molecular Neuroscience. 15. 243-250 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] R.Fujii: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"The Journal of Biological Chemistry. 276. 5445-5451 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Aratani: "Dual roles of RNA helicase A on CREB-dependent transcription"Molecular and Cellular Biology. 21. 4460-4469 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Daitoku: "Dimerization of small GTPase Rab5"International Journal of Molecular Medicine. 8. 397-404 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Kawabata: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium induced keratinocyte differentiation"The Journal of Biological Chemistry. 277. 8099-8105 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Nakazawa, H. Ishii, H. Aono, M. Takai, T. Honda, S. Aratani, A. Fukamizu, H. Nakamura, S-I, Yoshino, T. Kobata, K. Nishioka, T. Nakajima: "Role of Notch-1 intracellular domain in activation of rheumatoid synoviocytes"Arthritis and Rheumatism. 44. 1545-1554 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Nakazawa, S. Aratani, M. Hatta, N. Araya, H. Daitoku, K. Kawahara, S. Watanabe, H. Nakamura, S. Yoshino, A. Fukamizu, K. Nishioka, T. Nakajima: "TNF α induces acetylation of p53 but attenuates its transcriptionalactivation in rheumatoid synoviocytes"International Journal of Molecular Medicine. 10. 269-275 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakazawa M, Ishii H, Nakamura H, Yoshino S, Fukamizu A, Nishioka K, Nakajima T.: "NF□B2 (p52) promoter activation via Notch signaling pathway in rheumatoid synoviocytes"International Journal of Molecular Medicine. 7. 31-35 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakazawa M., Hasunuma T., Ohshima T., Tanaka Y., Nishioka k., Nakajima T.: "CBP : a target molecule of HTLV-1 Tax in synoviocyte activation"Biochem. Biophys. Res. Comm.. 269. 584-590 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Ishii, M. Nakazawa, S. Yoshino, H. Nakamura, K Nishioka, T. Nakajima: "Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patient"Rheumatology International. 21. 10-14 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Taniguchi, K. Kawahara, K. Yone, T. Hashiguchi, M. Yamakuchi, M. Goto, K. Inoue, S. Yamada, K. Ijiri, S.Matsunaga, T. Nakajima, S. Komiya, I. Maruyama: "High Mobility Group Box Chromosomal Protein 1 Plays a Role in the Pathogenesis of Rheumatoid Arthritis as a Novel Cytpkine"Arthritis and Rheumatism. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Hirose, R. Fujii, H. Nakamura, A. Aratani, H. Fujita, M. Nakazawa, K. Nakamura, K. Nishioka, T. Nakajima: "Regulation of CREB-mediated transcription by association of CDK4 binding protein p34 SEI-1 with CBP"International Journal of Molecular Medicine. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nguyen Dinh Khoa, Minako Nakazawa, Tomoko Hasunuma, Toshihiro Nakajima, Hiroshi Nakamura, Tetsuji Kobata, Kusuki Nishioka: "Potential role of HOXD9 in synoviocyte proliferation"Arthritis and Rheumatism. 44. 1013-1021 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nguyen Ngoc Chau, H. Nakamura, M. Nakazawa, T. Hirose, T. Kobata, K. Nishioka: "Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis patients"International Journal of Molecular Medicine. 10. 41-48 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohshima T, Yoshida Y, Nakajima T, Yagami K, Fukamizu A: "Effects of interaction between parvovirus minute virus of mice NS1 and coactivator CBP on NS1-and p53 -transactivation"International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] KP. Sarfcer, M. Nakata, I. Kitajima, T. Nakajima, I. Maruyama: "Inhibition of Caspase-3 Activation by SB203580, p38 Mitogen-Activated Protein Kinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells"Journal of Molecular Neuroscience. 15. 243-250 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] R Fujii, M Okamoto, S Aratani, T Oishi, T Ohshima, K Taira, M Baba, A Fukamizu, T. Nakajima: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"J Biol. Chem.. 276. 5445-5451 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S. Aratani, R. Fujii, T. Oishi, H. Fujita, T. Amano, T. Ohshima, M. Hagiwara, A. Fukamizu, and T. Nakajima: "Dual roles of RNA helicase A in CREB-dependent transcription"Mol.Cell.Biol.. 21. 4460-4469 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Daitoku, J. Ishida, K. Fujiwara, T. Nakajima. A. Fukamizu: "Dimerization of small GTPase Rab5"International Journal of Molecular Medicine. 8. 397-404 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Kawabata, K. Kawahara, T. Kanekura, N. Araya, H. Daitoku, M. Hatta, N. Miura, A. Fukamizu, T. Kanzaki, I. Maruyama, T. Nakajima: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium induced keratinocyte differentiation"J Biol. Chem.. 277. 8099-8105 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Nakazawa: "Role of Notch-1 intracellular domain in activation of rheumatoid Synoviocytes"Arthritis & Rheum. 44. 1545-1554 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Nakazawa: "NFkB2(p52)promoter pathway in rheumatoid synoviocytes"International Journal of Molecular Medicine. 10. 269-275 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakazawa M: "NF□B2(p52)promoter activation via Notch signaling pathway in rheumatoid synoviocytes"International Journal of Molecular Medicine. 7. 31-35 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakazawa M: "CBP : a target molecule of HTLV-1 Tax in synoviocyte activation"Biochem. Biophys. Res. Comm.. 269. 584-590 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Ishii: "Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients"Rheumatology International. 21. 10-14 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Taniguchi: "High Mobility Group Box Chromosomal Protein 1 Plays a Role in the Pathogenesis of Rheumatoid Arthritis as a Novel Cytokine"Arthritis and Rheumatism. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Hirose: "Regulation of CREB-mediated transcription by association of CDK4 binding protein p34 SEI-1 with CBP"International Journal of Molecular Medicine. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation"Arthritis & Rheum. 44. 1013-1021 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nguyen Ngoc Chau: "Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis patients"International Journal of Molecular Medicine. 10. 41-48 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Ohshima: "Effects of interaction between parvovirus minute virus of mice NS1 and p53-transactivation"International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] KP.Sarker: "Inhibition of Caspase-3 Activation by SB203580,p38 Mitogen-Activated ProteinKinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells"Journal of Molecular Neuroscieuce. 15. 243-250 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] R.Fujii: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"The Journal of Biological Chemistry. 276. 5445-5451 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Aratani: "Dual roles of RNA helicase A on CREB-dependent transcription"Molecular and Cellular Biology. 21. 4460-4469 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Daitoku: "Dimerization of small GTPase Rab5"International Journal of Molecular Medicine. 8. 397-404 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Kawabata: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium induced keratinocyte differentiation"The Journal of Biological Chemistry. 277. 8099-8105 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Nakazawa: "NFκB2 (p52) promoter pathway in rheumatoid synoviocytes"International Journal of Molecular Medicine. 7. 31-35 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Ohshima: "Effects of interaction between parvovirus minute virus of mice NS1 and p53-transactivation"International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] KP.Sarker: "Inhibition of Caspase-3 Activation by SB203580, p38 Mitogen-Activated ProteinKinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells"Journal of Molecular Neuroscience. 15. 243-250 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation"Arthritis & Rheum. 44. 1013-1021 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] R.Fujii: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"The Journal of Biological Chemistry. 276. 5445-5451 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Nakazawa: "Role of Notch-1 intracellular domain in activation of rheumatoid Synoviocytes"Arthritis & Rheum. 44. 1545-1554 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Aratani: "Dual roles of RNA helicase A on CREB-dependent transcription"Molecular and Cellular Biology. 21. 4460-4469 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Daitoku: "Dimerization of small GTPase Rab5"International Journal of Molecular Medicine. 8. 397-404 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Ishii: "Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients"Rheumatology International. 21. 10-14 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kawabata: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium induced keratinocyte differentiation"The Journal of Biological Chemistry. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Miyagishi: "Cell type-dependent transcactivation or repression of mesoderm-restricted basic helix-loop-helix protein, POD-1/Capsulin."Molecular and Cellular Biochemistry. 205. 141-147 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Miyagishi: "Molecular characterization of mesoderm-restricted basic helix-loop-helix protein, POD-1/capsulin."International Journal of Molecular Medicine. 5. 27-31 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Nakazawa: "CBP : a target molecule of HTLV-1 Tax in synoviocyte activation."Biochemical and Biophysical Research Communications. 269. 584-590 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jukka Pitk nen: "APECED protein AIRE has transcriptional transactivating properties and interacts with common co-activator CBP."The Journal of Biological Chemistry. 275. 6802-16809 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Simohata: "Interaction of expanded polyglutamine stretches associated with CAG repeat diseases and hTAFII130 interfereres with CREB-dependent transcription."Nature Genetics. 26. 29-36 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Miyagishi: "Regulation of Lef-mediated transcription and p53-dependent pathway by associatng β-catenin with CBP/p300."The Journal of Biological Chemistry. 275. 35170-35175 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Nakazawa: "NFκB2(p52) promoter pathway in rheumatoid synoviocytes."International Journal of Molecular Medicine. 7. 31-35 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Ohshima: "Effects of interaction between parvovirus minute virus of mice NS1 and p53-transactivation."International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] KP.Sarker: "Inhibition of Caspase-3 Activation by SB203580, p38 Mitogen-Activated ProteinKinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells."Journal of Molecular Neuroscience. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation."Arthritis & Rheum. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] R.Fujii: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"The Journal of Biological Chemistry. 276. 5445-5451 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Nakazawa: "Role of Notch-1 intracellular domain in activation of rheumatoid Synoviocytes."Arthritis & Rheum. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Satoko Aratani: "Dual roles of RNA helicase A on CREB-dependent transcription."Molecular and Cellular Biology. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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