1997 Fiscal Year Annual Research Report

選択的蛋白分解のメカニズム

Research Project

Project/Area Number	08278102
Research Institution	The University of Tokyo
Principal Investigator	鈴木紘一東京大学, 分子細胞生物学研究所, 教授 (80011948)
Co-Investigator(Kenkyū-buntansha)	木戸博徳島大学, 酵素科学研究センター, 教授 (50144978) 村上安子東京慈恵会医科大学医学部, 教授 (30056709) 佐方功幸九州大学理学部, 教授 (80142024) 山尾文明国立遺伝学研究所, 助教授 (10158074) 田中啓二東京都臨床医学総合研究所, 部長 (10108871)
Keywords	プロテオリシス / 蛋白分解 / プロテアーゼ / プロテアソーム / カルパイン / バイオモジュレーター
Research Abstract	現代生物学に残された最大の研究課題の1つである蛋白質の寿命決定機構の解明を目ざし、その基盤となる選択的な蛋白分解の分子機構とその生理機能の意義の解析を行っている。主にプロテアソームとカルパイン系に焦点を絞って研究を行うと共に、選択的な蛋白分解の異常に起因する様々な病的状態の解析を行い、その疾病の原因究明、治療法の開発に資することを目的とした。鈴木と牧はカルパイン系の蛋白分解系を検討し、骨格筋に特異的に発現するカルパインがコネクチンと特異的に相互作用すること、X線による結晶構造解析でカルパインにはカルシウムを結合するEFハンド構造がサブユニット当り5個存在し、EFハンド構造がダイマ形成で重要な役割を果たすことを明らかにした。田中、村上、佐方、山尾はプロテアソーム系の蛋白分解を独自の系で解析した。田中は内在性抗原のプロセシングにおけるプロテアソームの機能とプロリン残基の役割を明らかにした。山尾は細胞分裂期のサイクリンの分解に関係するプロテアソームとユビキチン結合酵素を同定した。佐方は卵成熱におけるcdk2キナーゼの制御因子cdc25Aのプロテアソームによる分解を解明した。村上はオルニチン脱炭酸酵素のプロテソームによる分解を調べ、分解におけるATPの作用と酵素の高次構造の変化の関係を明らかにした。木戸はエイズウィルスの細胞内侵入過程にはトリプターゼとヌクレオチド2リン酸(NDP)キナーゼが関係することを明らかにし、Hsp70などの分子シャペロンのATPase活性もNDPキナーゼ活性に由来することを予測した。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] K.Kinbara: "Muscle-specific calpain,p94,interacts with the extreme C-terminal region of connectin,a unique region flanked by two immunoglobulin C2 motifs." Arch.Biochem.Biophys.342. 99-107 (1997)
[Publications] H.Sorimachi: "Tissue-specific expression and alpha-actinin binding properties of the Z-disc titin:Implications for the nature of vertebrate Z-discs." J.Mal.Biol.270. 688-695 (1997)
[Publications] S.Amano: "Identification of Endogenous substrates for Drosophila calpain from a salt-extracted fraction of Drosophila ovaries." J.Biochem.122. 865-871 (1997)
[Publications] K.Kominami: "Yeast counterparts of subunits S5a and p58 (S3) of the human 26S Proteasome areencoded by two multicopy supressors of nin1-1." Mol.Biol.Cell.8. 171-187 (1997)
[Publications] Y.Makino: "SUG1,a component of the 26S proteasome,is an ATPase stimulated by specifie RNAs." J.Biol.Chem.272. 23201-23205 (1997)
[Publications] A.Saito: "cDNA cloning and functional analysis of p44.5 and p55,two regulatory subunits,of the 26s proteasome." Gene. 241-250 (1997)
[Publications] F.Osaka: "A ubiquitin-conjugating enzyme in fission yeast,that is essential for the onset of anaphase in mitosis." Mole.Cell.Biol.17. 3388-3397 (1997)
[Publications] T.Nakajima: "Introduction of Ubiquitin-Conjuguting Enzyme Activity for Degradation of Topoisomerase IIα during Adenovirus EIA-Induced Apoptosis." Biophys.Biochem.Res.Commun.239. 823-829 (1997)
[Publications] N.Sagata: "What does Mos do in oocytes and somatic cells?" BioEssays. 19. 13-21 (1997)
[Publications] N.Furuno: "Meiotic cell cycle in Xenopus oocytes is independent of cdk2 kinase" EMBO J.16. 3860-3865 (1997)
[Publications] K.Koguchi: "Involvement of antizyme-like regulatory protein in polyamine-caused repression of ornithine decarboxylase in insect-derived Trichoplusia ni 5 cells." Biochim.Biophys.Acta. 1357. 291-296 (1997)
[Publications] K.Koguchi: "Cloning and sequencing of a humen cDNA encoding ornithine decarboxylase antizume inhibitor." Biochim.Biophys.Acta. 1353. 209-216 (1997)
[Publications] M.Yano: "Intrinsic Nucleoside Diphosphate Kinase-like Activity as a Novel Function of 14-3-3 Proteins" FEBS Letters. 419. 244-248 (1997)
[Publications] H.Kido: "Molecular Besis of Proteolytic Activation of Sendai Virus Infection and the Defensive Compounds for Infection" Biol.Chem. 378. 255-263 (1997)
[Publications] Y.Beppu: "Human Mucus Protease Inhibitor in Airway Fluids is a Potential Defensive Compound against Infection with Influenza A and Sendai Viruses." J.Biochem.121(2). 309-316 (1997)
[Publications] T.Konno: "A circular dichroism study of preferential hydration and alcohol effects on a denatured protein,pig calpastatin domain." Biochim.Biophya.Acta. 1342. 73-82 (1997)
[Publications] Y.H.Choi: "Regulation of cyclin D1 by calpain protease." J.Biol.Chem. 272. 28479-28484 (1997)
[Publications] E.M.Vilei: "Functional properties of recombinant calpain I and of mutants lacking domains III and IV of the catalytic subunit." J.Biol.Chem.272. 25802-25808 (1997)

1997 Fiscal Year Annual Research Report

選択的蛋白分解のメカニズム

Principal Investigator

鈴木 紘一 東京大学, 分子細胞生物学研究所, 教授 (80011948)

Research Products

[Publications] K.Kinbara: "Muscle-specific calpain,p94,interacts with the extreme C-terminal region of connectin,a unique region flanked by two immunoglobulin C2 motifs." Arch.Biochem.Biophys.342. 99-107 (1997)

[Publications] H.Sorimachi: "Tissue-specific expression and alpha-actinin binding properties of the Z-disc titin:Implications for the nature of vertebrate Z-discs." J.Mal.Biol.270. 688-695 (1997)

[Publications] S.Amano: "Identification of Endogenous substrates for Drosophila calpain from a salt-extracted fraction of Drosophila ovaries." J.Biochem.122. 865-871 (1997)

[Publications] K.Kominami: "Yeast counterparts of subunits S5a and p58 (S3) of the human 26S Proteasome areencoded by two multicopy supressors of nin1-1." Mol.Biol.Cell.8. 171-187 (1997)

[Publications] Y.Makino: "SUG1,a component of the 26S proteasome,is an ATPase stimulated by specifie RNAs." J.Biol.Chem.272. 23201-23205 (1997)

[Publications] A.Saito: "cDNA cloning and functional analysis of p44.5 and p55,two regulatory subunits,of the 26s proteasome." Gene. 241-250 (1997)

[Publications] F.Osaka: "A ubiquitin-conjugating enzyme in fission yeast,that is essential for the onset of anaphase in mitosis." Mole.Cell.Biol.17. 3388-3397 (1997)

[Publications] T.Nakajima: "Introduction of Ubiquitin-Conjuguting Enzyme Activity for Degradation of Topoisomerase IIα during Adenovirus EIA-Induced Apoptosis." Biophys.Biochem.Res.Commun.239. 823-829 (1997)

[Publications] N.Sagata: "What does Mos do in oocytes and somatic cells?" BioEssays. 19. 13-21 (1997)

[Publications] N.Furuno: "Meiotic cell cycle in Xenopus oocytes is independent of cdk2 kinase" EMBO J.16. 3860-3865 (1997)

[Publications] K.Koguchi: "Involvement of antizyme-like regulatory protein in polyamine-caused repression of ornithine decarboxylase in insect-derived Trichoplusia ni 5 cells." Biochim.Biophys.Acta. 1357. 291-296 (1997)

[Publications] K.Koguchi: "Cloning and sequencing of a humen cDNA encoding ornithine decarboxylase antizume inhibitor." Biochim.Biophys.Acta. 1353. 209-216 (1997)

[Publications] M.Yano: "Intrinsic Nucleoside Diphosphate Kinase-like Activity as a Novel Function of 14-3-3 Proteins" FEBS Letters. 419. 244-248 (1997)

[Publications] H.Kido: "Molecular Besis of Proteolytic Activation of Sendai Virus Infection and the Defensive Compounds for Infection" Biol.Chem. 378. 255-263 (1997)

[Publications] Y.Beppu: "Human Mucus Protease Inhibitor in Airway Fluids is a Potential Defensive Compound against Infection with Influenza A and Sendai Viruses." J.Biochem.121(2). 309-316 (1997)

[Publications] T.Konno: "A circular dichroism study of preferential hydration and alcohol effects on a denatured protein,pig calpastatin domain." Biochim.Biophya.Acta. 1342. 73-82 (1997)

[Publications] Y.H.Choi: "Regulation of cyclin D1 by calpain protease." J.Biol.Chem. 272. 28479-28484 (1997)

[Publications] E.M.Vilei: "Functional properties of recombinant calpain I and of mutants lacking domains III and IV of the catalytic subunit." J.Biol.Chem.272. 25802-25808 (1997)

鈴木紘一東京大学, 分子細胞生物学研究所, 教授 (80011948)