2000 Fiscal Year Annual Research Report

抗アセチル化リジン抗体による新たなる核内調節機構の研究

Research Project

Project/Area Number	11878130
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	転写統合装置 / アセチル基転移酵素 / 動脈硬化症 / 血管平滑筋細胞 / トロンビン / 細胞増殖 / CREB結合蛋白質CBP)
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(Nature Genetics2000,JBC2000,2001,Cell1996,1997、Nature1996、MCB1996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。最近、これら転写統合装置分子群にヒストンをはじめとする核内因子に対するアセチル基転移酵素活性が存在することが報告された。これらの研究成果に基づき、転写統合装置機能、とくにその酵素活性をモニターするために抗アセチル化リジン抗体を作成した。本抗体により核内アセチル化シグナルの検証が可能となった。さらに動脈硬化症の病巣血管平滑筋細胞では増殖シグナルに伴い核内アセチル化シグナルが有意に亢進していることを世界に先駆け発見した(BBRC1999)。現在、同抗体を用い、動脈硬化症のみならず種々の疾患の病態と核内アセチル化が関連していること、及び新規核内アセチル化タンパク質の同定が進行している。今後、これらの解析により同抗体の有用性が確証されることが期待される。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] H.Shin: "Thrombin receptor mediated signals induce expressions of interleukin 6 andgranulocyte colony stimulating factor via NF-kB activation in synovial fibroblasts."Annals of the Rheumatic Diseases. 58. 55-60 (1999)
[Publications] J.Ishida: "Expression andcharacterization of mouse angiotensin II type 1a receptor tagginghemagglutinin epitope in cultured cells."International Journal of Molecular Medicine. 3. 263-270 (1999)
[Publications] F.Ukaji: "Serum samples of patientswith rheumatoid arthritiscontain a specific autoantibody to "denatured" aldolase A in theosteoblast-like cell line, MG-63."Annals of the Rheumatic Diseases. 58. 169-174 (1999)
[Publications] K.P.Sarker: "Serum Prevents Thrombin-induced Mouse Neuroblastoma Cell Death."J.Kagoshima Conference on Cerebrovascular disease. 1. 95-99 (1999)
[Publications] K.P.Sarker: "Inhibition of Thrombin-induced Neural Cell Death by Recombinant Thrombomodulin andE5510, a Synthetic Thrombin Receptor Signaling Inhibitor."Thrombosis and Haemostasis. 82. 1071-1077 (1999)
[Publications] T.Oshima: "CRM1 mediates nuclea export of parvovirus minute virus of mice nonstructural protein NS2."Biochemical and Biophysical Research Communications. 264. 144-150 (1999)
[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 hTAFII130 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] K.P.Sarker: "Increased Production of Vascular Endothelial Growth Factor (VEGF) by"Neurosci.Research Communications. 25. 79-88 (1999)
[Publications] K.P.Sarker: "Inhibition of Nitric oxide (NO)-induced Neuronal Cells Death by Epinephrine."Neurosci.Research Communications. 25. (1999)
[Publications] D.Koya: "Overexpression of Core 2 N-acetylglycosaminyltransferase Enhanced Cytokine Actions and Induced Hypertrophic Myocardium in Transgenic Mice."The FASEB Journal. 13. 2329-2337 (1999)
[Publications] K-I.Kawahara: "Hypernuclear acetylation in atherosclerotic lesions and activated vascular smooth muscle cells."Biochemical and Biophysical Research Communications. 266. 417-424 (1999)
[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)

2000 Fiscal Year Annual Research Report

抗アセチル化リジン抗体による新たなる核内調節機構の研究

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] H.Shin: "Thrombin receptor mediated signals induce expressions of interleukin 6 andgranulocyte colony stimulating factor via NF-kB activation in synovial fibroblasts."Annals of the Rheumatic Diseases. 58. 55-60 (1999)

[Publications] J.Ishida: "Expression andcharacterization of mouse angiotensin II type 1a receptor tagginghemagglutinin epitope in cultured cells."International Journal of Molecular Medicine. 3. 263-270 (1999)

[Publications] F.Ukaji: "Serum samples of patientswith rheumatoid arthritiscontain a specific autoantibody to "denatured" aldolase A in theosteoblast-like cell line, MG-63."Annals of the Rheumatic Diseases. 58. 169-174 (1999)

[Publications] K.P.Sarker: "Serum Prevents Thrombin-induced Mouse Neuroblastoma Cell Death."J.Kagoshima Conference on Cerebrovascular disease. 1. 95-99 (1999)

[Publications] K.P.Sarker: "Inhibition of Thrombin-induced Neural Cell Death by Recombinant Thrombomodulin andE5510, a Synthetic Thrombin Receptor Signaling Inhibitor."Thrombosis and Haemostasis. 82. 1071-1077 (1999)

[Publications] T.Oshima: "CRM1 mediates nuclea export of parvovirus minute virus of mice nonstructural protein NS2."Biochemical and Biophysical Research Communications. 264. 144-150 (1999)

[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 hTAFII130 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] K.P.Sarker: "Increased Production of Vascular Endothelial Growth Factor (VEGF) by"Neurosci.Research Communications. 25. 79-88 (1999)

[Publications] K.P.Sarker: "Inhibition of Nitric oxide (NO)-induced Neuronal Cells Death by Epinephrine."Neurosci.Research Communications. 25. (1999)

[Publications] D.Koya: "Overexpression of Core 2 N-acetylglycosaminyltransferase Enhanced Cytokine Actions and Induced Hypertrophic Myocardium in Transgenic Mice."The FASEB Journal. 13. 2329-2337 (1999)

[Publications] K-I.Kawahara: "Hypernuclear acetylation in atherosclerotic lesions and activated vascular smooth muscle cells."Biochemical and Biophysical Research Communications. 266. 417-424 (1999)

[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)

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)