1989 Fiscal Year Annual Research Report

多機能プロテアーゼ復合体(プロテアソーム)の機能と癌化における異常発現機構の解析

Research Project

Project/Area Number	01015071
Research Institution	The University of Tokushima
Principal Investigator	市原明徳島大学, 酵素科学研究センター, 教授 (40035374)
Co-Investigator(Kenkyū-buntansha)	富田優美子徳島大学, 酵素科学研究センター, 助手 (00089913) 田中啓二徳島大学, 酵素科学研究センター, 助手 (10108871) 野田千征子徳島大学, 酵素科学研究センター, 助教授 (40035506)
Keywords	プロテアソーム / 多機能プロテアーゼ / がん細胞 / 細胞増殖 / 異常発現 / 白血病細胞 / 蛋白復合体
Research Abstract	ラット肝臓からプロテアソームを分離純化し、そのサブユニットの中からCー2ー9を選び数ケのペプチドのアミノ酸配列を決定し、それからcDNAを得て、これらサブユニットの推定されるアミノ酸配列を決定した。しかし既存の蛋白構造とは全ったく相同性を示さなかった。この両cDNAを用いて各種ヒト白血病細胞培養株での発現を検討したところ、正常リンバ球、単球に比し異常に高い発現を見た。正常リンパ球をフィトヘモアグルチニンで幼若化させても増加した。また白血病患者骨膸組織をこれらサブユニット抗体で染めても高い発現を認めた。次にラット肝癌培養株、ヒト原発肝癌で検討したがやはり正常肝臓に比し高い発現であった。しかしラットの肝部分切除後の再生中や初代培養ラット肝細胞をEGF添加で増殖させた場合では正常値と同じであった。また生直後の新生仔肝でも変らなかった。これらの結果はプロテアソームの機能は正常増殖よりむしろ異常増殖に密接に関係している事を示唆しているが、その機構の詳細は未だ不明である。最近がん患者血清中にはこの酵素が著しく漏出している事を認め、またがん部の手術的摘除によりこの値が減少することも明らかとなった。これからは更に例数をふやし癌の種類、組織の種類、漏出の機構等を検討しがん診断との応用化を確立したい。しかしこの研究課題の根本はこの酵素の機能の解明であり、今後は酵母の分裂機構との関与を標的にし、その本質的解明も行ないたい。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Fujiwara,T.: "Molecular cloning cDNA for proteasomes(multiーcatalytic proteinase complexes)from rat liver:primary strucuture of the largest subunit(C2)" Biochemistry. 28. 7332-7340 (1989)
[Publications] Seol,J.H.: "Na^+,K^+ーspecific inhibition of protein and peptide hydrolyses by proteasomes from human hepatoma tissues" FEBS Letter. 247. 197-200 (1989)
[Publications] Tanaka,K.: "Helfーlife of proteasomes(Multiーproteases complexes)in rat liver" Biochemical Biophysical Research Communication. 159. 1309-1315 (1989)
[Publications] Matthews,W.: "Involvement of the proteasome in different degradative processes in mammalian cells" Proceedings of National Academy of Sciences,USA. 86. 2597-2601 (1989)
[Publications] Inoue,C.: "Nicotinamide prolongs survival of primary cultured hepatocytes without involving loss of hepatocyteーspecific functions" Journal of Biological Chemistry. 264. 4747-4750 (1989)
[Publications] Okada,F.: "purification and structure analysis of a latent form of transforming growth factorーp from rat platelets" Journal of Biochemistry. 106. 304-310 (1989)
[Publications] Tanaka,K.: "Role of substrate in reversible activation of proteasomes(Multiーprotease complexes)by sodium dodesyl sulfate" Journal of Biochemistry. 106. 495-500 (1989)
[Publications] Eukaryotic proteasome: "Eukaryotic proteasomes(20S ringーshaped particles withmultiple protease complexes)" Intracellular proteolysis(Eds.Katunuma,N.et al.)Japanese Science Society Press,Tokyo. 233-240 (1989)
[Publications] Ichihara,A.: "Hormonal regulation of gene expressions in primary cultured hepatoーcytes and its relation with cell growth" Proceedings of Conference on Molecular Biology and Gene Engineerings. 4. 16-20 (1989)
[Publications] Tanaka,K.: "Separation of yeast proteasome subunits,Immunoreactivity with antibodies against ATPーdependent protease Ti from Escherichia coli" Biochemical and Biophysical Research Communication. 164. 1253-1261 (1989)
[Publications] Okada,F.: "One of two subunits of masking protein in latent TGFーbeta is a part of proーTGFーbeta" FEBS Letter. 242. 240-242 (1989)
[Publications] Tanaka,K.: "Direct evidence for nuclear and cytoplasmic coーlocalization of proteasomes(Multiーprotease complexes)in liver" Journal of Cellular physiology. 139. 34-41 (1989)
[Publications] Arakaki,R.: "Reciprocal,cell density dependent inhibitions of growth of rat hepatocytes in primary cultures by transforming growthーfactorーb and interleukinー1beta" Experimental Cell Research. (1990)
[Publications] Kanda,S.: "Negative regulation of autonomous growth of neonatal rat hepatocytes in primary culture by interleukins and betaーtype transforming growth factor" Cancer Research. (1990)
[Publications] Ichihara,A.: "Nutrition:Protein and Amino Acid(Eds.Naito,H.et al.)(Japanese Science Promotion Society Press,Tokyo)" Regulation of protein and amino acid metabolism in cultured hepatocytes, 49-65 (1990)
[Publications] Ichihara,A.: "Normal and Neoplastic growth in Hepatology(Eds.Francavilla,A.)" Mechanisms controlling growth of hepatocytes in Primary culture, (1990)

1989 Fiscal Year Annual Research Report

多機能プロテアーゼ復合体(プロテアソーム)の機能と癌化における異常発現機構の解析

Principal Investigator

市原 明 徳島大学, 酵素科学研究センター, 教授 (40035374)

Research Products

[Publications] Fujiwara,T.: "Molecular cloning cDNA for proteasomes(multiーcatalytic proteinase complexes)from rat liver:primary strucuture of the largest subunit(C2)" Biochemistry. 28. 7332-7340 (1989)

[Publications] Seol,J.H.: "Na^+,K^+ーspecific inhibition of protein and peptide hydrolyses by proteasomes from human hepatoma tissues" FEBS Letter. 247. 197-200 (1989)

[Publications] Tanaka,K.: "Helfーlife of proteasomes(Multiーproteases complexes)in rat liver" Biochemical Biophysical Research Communication. 159. 1309-1315 (1989)

[Publications] Matthews,W.: "Involvement of the proteasome in different degradative processes in mammalian cells" Proceedings of National Academy of Sciences,USA. 86. 2597-2601 (1989)

[Publications] Inoue,C.: "Nicotinamide prolongs survival of primary cultured hepatocytes without involving loss of hepatocyteーspecific functions" Journal of Biological Chemistry. 264. 4747-4750 (1989)

[Publications] Okada,F.: "purification and structure analysis of a latent form of transforming growth factorーp from rat platelets" Journal of Biochemistry. 106. 304-310 (1989)

[Publications] Tanaka,K.: "Role of substrate in reversible activation of proteasomes(Multiーprotease complexes)by sodium dodesyl sulfate" Journal of Biochemistry. 106. 495-500 (1989)

[Publications] Eukaryotic proteasome: "Eukaryotic proteasomes(20S ringーshaped particles withmultiple protease complexes)" Intracellular proteolysis(Eds.Katunuma,N.et al.)Japanese Science Society Press,Tokyo. 233-240 (1989)

[Publications] Ichihara,A.: "Hormonal regulation of gene expressions in primary cultured hepatoーcytes and its relation with cell growth" Proceedings of Conference on Molecular Biology and Gene Engineerings. 4. 16-20 (1989)

[Publications] Tanaka,K.: "Separation of yeast proteasome subunits,Immunoreactivity with antibodies against ATPーdependent protease Ti from Escherichia coli" Biochemical and Biophysical Research Communication. 164. 1253-1261 (1989)

[Publications] Okada,F.: "One of two subunits of masking protein in latent TGFーbeta is a part of proーTGFーbeta" FEBS Letter. 242. 240-242 (1989)

[Publications] Tanaka,K.: "Direct evidence for nuclear and cytoplasmic coーlocalization of proteasomes(Multiーprotease complexes)in liver" Journal of Cellular physiology. 139. 34-41 (1989)

[Publications] Arakaki,R.: "Reciprocal,cell density dependent inhibitions of growth of rat hepatocytes in primary cultures by transforming growthーfactorーb and interleukinー1beta" Experimental Cell Research. (1990)

[Publications] Kanda,S.: "Negative regulation of autonomous growth of neonatal rat hepatocytes in primary culture by interleukins and betaーtype transforming growth factor" Cancer Research. (1990)

[Publications] Ichihara,A.: "Nutrition:Protein and Amino Acid(Eds.Naito,H.et al.)(Japanese Science Promotion Society Press,Tokyo)" Regulation of protein and amino acid metabolism in cultured hepatocytes, 49-65 (1990)

[Publications] Ichihara,A.: "Normal and Neoplastic growth in Hepatology(Eds.Francavilla,A.)" Mechanisms controlling growth of hepatocytes in Primary culture, (1990)

市原明徳島大学, 酵素科学研究センター, 教授 (40035374)