2000 Fiscal Year Annual Research Report

核内転写統合装置を用いた血管平滑筋細胞特異的転写因子の同定

Research Project

Project/Area Number	12032201
Research Institution	St. Marianna University School of Medicine
Principal Investigator	中島利博聖マリアンナ医科大学, 難病治療研究センター, 助教授 (90260752)
Co-Investigator(Kenkyū-buntansha)	深水昭吉筑波大学, 応用生物化学系, 教授 (60199172)
Keywords	血管平滑筋細胞 / 転写統合装置 / CREB結合蛋白質(CBP) / 転写因子 / 分化抑制因子(Id) / yeast2-hybrid法 / アセチル化 / Helix-loop-helixモチーフ
Research Abstract	私たちを含む幾つかの研究グループによりCBP(CREB binding protein)をはじめとする転写コアクチベーターの機能解析が進められた(Cell 1996&1997など)。さらに、転写コアクチベーター分子が複数のシグナル伝達系の協調・拮抗の最終ターゲットとして存在し、シグナル伝達の多様性・巧緻性を規定していること。また、細胞増殖・分化・アポトーシスなどの非常に多くの生物学的現象に関与していることが示された。これらのことより、わたしたちは転写コアクチベーターをコンピューターの集積回路(IC)に相当すると考え転写統合装置と命名した(Nature 1996)。これらの研究成果に基づき、転写コアクチベーターの統合装置機能を利用し、動脈硬化病巣を規定する核内因子のクローニングを試みた。その結果、血管平滑筋細胞に比較的特異的発現しているヘリックス-ループ-ヘリックスタイプの転写因子POD-1/Capsulin、Id様因子などが得られた。これらの因子が血管平滑筋細胞の分化・増殖を規定している可能性について今後、研究の継続が必要であろう。一方、転写統合装置に存在するアセチル化酵素活性を臨床検体でモニターするために、アセチル化リジン抗体を作成した。本抗体を用い、動脈硬化症などの病巣組織の核内アセチル化の程度を検証した。その結果、動脈硬化症の病巣血管平滑筋細胞では核内アセチル化シグナルが有意に亢進していることを発見した(BBRC 1999)。今後、本現象を標的とした動脈硬化治療法への開発への可能性を検証したい。

Research Products

(13 results)

All Other

All Publications (13 results)

[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)
[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)
[Publications] M.Nakazawa: "CBP : a target molecule of HTLV-1 Tax in synoviocyte activation."Biochemical and Biophysical Research Communications. 269. 584-590 (2000)
[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)
[Publications] T.Simohata: "Interaction of expanded polyglutamine stretches associated with CAG repeat diseases and hTAFll 130 interfereres with CREB-dependent transcription."Nature Genetics. 26. 29-36 (2000)
[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)
[Publications] M.Nakazawa: "NFκB2 (p52) promoter pathway in rheumatoid synoviocytes."International Journal of Molecular Medicine. 7. 31-35 (2001)
[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)
[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)
[Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation."Arthritis& Rheum. (in press). (2001)
[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)
[Publications] M.Nakazawa: "Role of Notch-1 intracellular domain in activation of rheumatoid Synoviocytes."Arthritis& Rheum. (in press). (2001)
[Publications] Satoko Aratani: "Dual roles of RNA helicase A on CREB-dependent transcription."Molecular and Cellular Biology. (in press). (2001)

2000 Fiscal Year Annual Research Report

核内転写統合装置を用いた血管平滑筋細胞特異的転写因子の同定

Principal Investigator

中島 利博 聖マリアンナ医科大学, 難病治療研究センター, 助教授 (90260752)

Research Products

[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)

[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)

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

[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)

[Publications] T.Simohata: "Interaction of expanded polyglutamine stretches associated with CAG repeat diseases and hTAFll 130 interfereres with CREB-dependent transcription."Nature Genetics. 26. 29-36 (2000)

[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)

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

[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)

[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)

[Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation."Arthritis& Rheum. (in press). (2001)

[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)

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

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

中島利博聖マリアンナ医科大学, 難病治療研究センター, 助教授 (90260752)