1994 年度実績報告書

G1/S期移行期の制御

研究課題

研究課題/領域番号	05269101
研究機関	東京大学
研究代表者	東江昭夫東京大学, 大学院・理学系研究科, 教授 (90029249)
研究分担者	南康博大阪大学, 細胞生体工学センター, 助手 (70229772) 吉田稔東京大学, 農学部, 助教授 (80191617) 田中一馬大阪大学, 医学部, 講師 (60188290) 荒木弘之大阪大学, 微生物病研究所, 教授 (20151160) 宮川都吉広島大学, 工学部, 教授 (10116676)
キーワード	細胞周期 / 信号伝達 / 出芽酵母 / 線維芽細胞 / IL-2 / 低分子量G蛋白質 / DNA複製
研究概要	出芽酵母のM期終了に係わる低分子量GTPase、Tem1、の作用を分子遺伝学的に調べた結果、Tem1はCdc15プロテインキナーゼを活性化することを通してCdc28キナーゼの活性を低下させることがわかった。M期で働く多くの遺伝子間の遺伝子的相互作用を調べ、それらの作用のネットワークのモデルを提唱した(東江)。出芽酵母の高濃度の塩への適応はプロテインキナーゼAの不活化とカルシニューリンの活性化により制御され、この機構がNa^+排出ポンプをコードするPMR2遺伝子の転写活性化レベルで利いていることを明らかにした(宮川)。出芽酵母のRho1低分子量GTPase遺伝子の温度感受性突然変異体をサプレスする優性変異体を分離した。RHO1遺伝子に優性活性型変異を導入し、この変異をサプレスするマルチコピーサプレッサーを分離し解析中である(田中)。IL-2受容体(IL-2R)と物理的、機能的に共役するチロシンキナーゼ(PTK)として、LckPTKに加えて新たにSykPTK,Jak1およびJak2PTKsを同定した。SykPTKがIL-2によるc-myc遺伝子の発現誘導に重要な役割を担うこと、さらに、Jak1およびJak2PTKsがIL-2刺激に伴うG1期からS期への進行に重要な役割を担うことを示唆した(南)。出芽酵母DNAポリメラーゼIIの80kDaサブユニットの温度感受性変異dpb2-1のマルチコピーサプレッサーMDB1遺伝子を分離した。Mdb1は分裂酵母のチェックポイント機構に関与するCut5に似ていた。またMDB1は増殖に必須であったため、mdb1の温度感受性株を作成して調べたところ、Mdb1がDNAポリメラーゼIIと相互作用してDNA複製を進めるとともに、S期のチェックポイント機構を通して細胞終期を調節していることが示唆された(荒木)。プロテインキナーゼ阻害剤スタウロスポリンによってS期に停止したCHO細胞は未成熟分裂、3Y1細胞はアポトーシスが誘導されるが、このときCHOではp34^<CDC2>が活性化されるが、3Y1では活性化されない。分裂酵母のレプトマイシンb耐性遺伝子をクローニングしたところ、これは分裂酵母の染色体高次構造維持に関与すると考えられるCrm1であった。ヒストンデアセチラーゼを特異的に阻害するトリコスタチンによって誘導される蛋白質として、アクチン調節蛋白質ゲルゾリンとヒストンバリアントH1^0を同定した。

研究成果

(32件)

すべてその他

すべて文献書誌 (32件)

[文献書誌] Shirayama,M.et al.: "Isolation of a CDC25 family gene,MSI2/LTE1,as a multicopy suppressor of iral." Yeast. 10. 451-461 (1994)
[文献書誌] Kawamura,D.et al.: "Cloning and Nucleotide sequence of a gene conferring ability to grow at a low temperature on Saccharomyces cerevisiae tryptophan auxotrophs." J.Ferm.Bioeng.77. 1-9 (1994)
[文献書誌] Kominami,K.et al.: "Characterization of the function of the NIN1 gene product of Saccharomyces cerevisiae." Exp.Cell Res.211. 203-211 (1994)
[文献書誌] Shirayama,M.et al.: "The yeast TEM1 gene,which encodes a GTP-binding protein,is involved in termination of M phase." Mol.Cell.Biol.14. 7476-7482 (1994)
[文献書誌] Ikeda,E.et al.: "YGE1 is yeast homologue of Escherichia coli grpE and is required for maintenance of mitochondrial functions." FEBS Lett.339. 265-268 (1994)
[文献書誌] Yoshida,M.et al.: "Cloning and sequencing of the NES24 gene of Saccharomyces cerevisiae." Yeast. 10. 371-376 (1994)
[文献書誌] Ando,T.et al.: "Molecular Cloning of the plcl^+ gene of Schizosaccharomyces pombe,which encodes a putative phosphoinositide-specific phospholipase C." Yeast. 11. 179-185 (1995)
[文献書誌] Hirata,D et al.: "Stress・induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the jun family of transcriptional activation in Saccharomyces cerevisiae" Mol.Gen.Genet.242. 250-256 (1994)
[文献書誌] Hirata,D.et al.: "Saccharomyces cerevisiae YDR1,which encodes a member of the ATP・binding cassette(ABC),superfamily.is required for multidrug resistance" Curr.Genet.26. 285-294 (1994)
[文献書誌] Taguchi,N.et al.: "Identification and analysis of the Saccharomyces cerevisiae SYR1 gene reveals that ergosterol is involved in the action of syringomycin" Microbiolgy. 140. 353-359 (1994)
[文献書誌] Araki,H.et al.: "The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae." Nucl.Acids Res.22. 1527-1535 (1994)
[文献書誌] Araki,H.et al.: "Hacl:A novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe." Nucl.Acids Res.22. 5279-5288 (1994)
[文献書誌] Masuda,T.,et.al.: "Molecular cloning and characterization of yeast rho GDP dissociation inhibitor." J.Biol.Chem.269. 19713-19718 (1994)
[文献書誌] Yamochi,W.,et.al.: "Growth site-localization of Rho1 small GTP-binding protein and its involvement in bud formation in Saccharomyces cerevisiae." J.Cell Biol.125. 1077-1093 (1994)
[文献書誌] Fujimura,K.,et.al.: "The Saccharomyces cerevisiae MSI4 gene encodes the yeast counterpart of component A of rab geranylgeranyltransferase." J.Biol.Chem.269. 9205-9212 (1994)
[文献書誌] Wood,R.,Douglas,et.al.: "Biochemical Characterization of yeast RAS2 mutants reveals a new region of ras protein involved in the interaction with GTPase-activating proteins." J.Biol.Chem.269. 5322-5327 (1994)
[文献書誌] Shirayama,M.,et.al.: "Isolation of a CDC25 family gene,MSI2/LTE1,as a multicopy suppressor of iral." YEAST・. 10. 451-461 (1994)
[文献書誌] Nishi et al.: "Leptomycin B targets a regulatory cascade of crml,a fission yeast nuclear protein,involved in control of higher order chromosome structure and gene expression." Journal of Biological Chemistry. 269. 6320-6324 (1994)
[文献書誌] Hoshikawa et al.: "Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines." Experimental Cell Research. 214. 189-197 (1994)
[文献書誌] Giardot et al.: "Relationship between core histone acetylation and histone Hl^0 gene activity." European Journal of Biochemistry. 224. 885-892 (1994)
[文献書誌] Yen et al.: "Enhanced cell differentiation when RB is hypophosphorylated and down-regulated by radicicol,a SRC-kinase inhibitor." Experimental Cell Research. 214. 163-171 (1994)
[文献書誌] Schlake et al.: "Gene expression within a chromatin domain:the role of core histone hyperacetylation." Biochemistry. 33. 4197-4206 (1994)
[文献書誌] Yoshida et al.: "Trichostatin A and trapoxin:novel chemical probes for the role of histone acetylation in chromatin structure and function." BioEssays. in press. (1995)
[文献書誌] Minami,Y.et al.: "Signal transduction mediated by the reconstituted IL-2 receptor: evidence for a cell type-specific function of IL-2 receptor B chain." J.Immunol.152. 5680-5690 (1994)
[文献書誌] Kawahara,Y.et al.: "Evidence for a critical role for the cytoplasmic region of the interleukin2 (IL-2) receptor γchain in IL-2,IL-4,and IL-7 signalling." Mol.Cell.Biol.14. 5433-5440 (1994)
[文献書誌] Miyazaki,T.et al.: "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits." Science. 266. 1045-1047 (1994)
[文献書誌] Minami,Y.et al.: "Protein typrosine kinase Syk is associated with and activated by the IL-2 receptor: possible 1ink with the c-myc induction pathway." Immunity. 2. 89-100 (1995)
[文献書誌] Minami,Y.et al.: "The IL-2 signalling; recruitment and activation of multiple protein tyrosin kinases by the IL-2 receptor components." Curr.Op.Cell Biol.(in press). (199)
[文献書誌] 宮川都吉ら (編・著): "酵母に見る最新の真核生物像酵母実験系への誘い担当部分:酵母のストレス応答とカルシニューリン" 東江の編, 共立出版, 489 (1994)
[文献書誌] 宮川都吉ら (編・著): "酵母とバイオ酵母研究の新潮流担当部分:酵母におけるカルシウム依存性プロテインホスファターゼの生理機能" 福井作蔵、高木正道監修 (財)日本バイオインダストリー協会編集, 医学出版センター, 305 (1994)
[文献書誌] Takai,Y.,et al.: "Proceedings of 24th International Symposium of the Princess Takamatsu Cancer Research Fund,Molecular and cellular basis for cell to cell interactions; its significance in cancer" Princeton Scientific Publishing Co.,Inc.,Princeton,U.S.A., (1994)
[文献書誌] Takai,Y.,et al.: "Molecular Nerobiology; Mecahnism Common to Brain,Skin,and Immune System" John Willy & Sons,Inc.,Toronto, 247 (1994)

1994 年度 実績報告書

G1/S期移行期の制御

研究代表者

東江 昭夫 東京大学, 大学院・理学系研究科, 教授 (90029249)

研究成果

[文献書誌] Shirayama,M.et al.: "Isolation of a CDC25 family gene,MSI2/LTE1,as a multicopy suppressor of iral." Yeast. 10. 451-461 (1994)

[文献書誌] Kawamura,D.et al.: "Cloning and Nucleotide sequence of a gene conferring ability to grow at a low temperature on Saccharomyces cerevisiae tryptophan auxotrophs." J.Ferm.Bioeng.77. 1-9 (1994)

[文献書誌] Kominami,K.et al.: "Characterization of the function of the NIN1 gene product of Saccharomyces cerevisiae." Exp.Cell Res.211. 203-211 (1994)

[文献書誌] Shirayama,M.et al.: "The yeast TEM1 gene,which encodes a GTP-binding protein,is involved in termination of M phase." Mol.Cell.Biol.14. 7476-7482 (1994)

[文献書誌] Ikeda,E.et al.: "YGE1 is yeast homologue of Escherichia coli grpE and is required for maintenance of mitochondrial functions." FEBS Lett.339. 265-268 (1994)

[文献書誌] Yoshida,M.et al.: "Cloning and sequencing of the NES24 gene of Saccharomyces cerevisiae." Yeast. 10. 371-376 (1994)

[文献書誌] Ando,T.et al.: "Molecular Cloning of the plcl^+ gene of Schizosaccharomyces pombe,which encodes a putative phosphoinositide-specific phospholipase C." Yeast. 11. 179-185 (1995)

[文献書誌] Hirata,D et al.: "Stress・induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the jun family of transcriptional activation in Saccharomyces cerevisiae" Mol.Gen.Genet.242. 250-256 (1994)

[文献書誌] Hirata,D.et al.: "Saccharomyces cerevisiae YDR1,which encodes a member of the ATP・binding cassette(ABC),superfamily.is required for multidrug resistance" Curr.Genet.26. 285-294 (1994)

[文献書誌] Taguchi,N.et al.: "Identification and analysis of the Saccharomyces cerevisiae SYR1 gene reveals that ergosterol is involved in the action of syringomycin" Microbiolgy. 140. 353-359 (1994)

[文献書誌] Araki,H.et al.: "The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae." Nucl.Acids Res.22. 1527-1535 (1994)

[文献書誌] Araki,H.et al.: "Hacl:A novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe." Nucl.Acids Res.22. 5279-5288 (1994)

[文献書誌] Masuda,T.,et.al.: "Molecular cloning and characterization of yeast rho GDP dissociation inhibitor." J.Biol.Chem.269. 19713-19718 (1994)

[文献書誌] Yamochi,W.,et.al.: "Growth site-localization of Rho1 small GTP-binding protein and its involvement in bud formation in Saccharomyces cerevisiae." J.Cell Biol.125. 1077-1093 (1994)

[文献書誌] Fujimura,K.,et.al.: "The Saccharomyces cerevisiae MSI4 gene encodes the yeast counterpart of component A of rab geranylgeranyltransferase." J.Biol.Chem.269. 9205-9212 (1994)

[文献書誌] Wood,R.,Douglas,et.al.: "Biochemical Characterization of yeast RAS2 mutants reveals a new region of ras protein involved in the interaction with GTPase-activating proteins." J.Biol.Chem.269. 5322-5327 (1994)

[文献書誌] Shirayama,M.,et.al.: "Isolation of a CDC25 family gene,MSI2/LTE1,as a multicopy suppressor of iral." YEAST・. 10. 451-461 (1994)

[文献書誌] Nishi et al.: "Leptomycin B targets a regulatory cascade of crml,a fission yeast nuclear protein,involved in control of higher order chromosome structure and gene expression." Journal of Biological Chemistry. 269. 6320-6324 (1994)

[文献書誌] Hoshikawa et al.: "Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines." Experimental Cell Research. 214. 189-197 (1994)

[文献書誌] Giardot et al.: "Relationship between core histone acetylation and histone Hl^0 gene activity." European Journal of Biochemistry. 224. 885-892 (1994)

[文献書誌] Yen et al.: "Enhanced cell differentiation when RB is hypophosphorylated and down-regulated by radicicol,a SRC-kinase inhibitor." Experimental Cell Research. 214. 163-171 (1994)

[文献書誌] Schlake et al.: "Gene expression within a chromatin domain:the role of core histone hyperacetylation." Biochemistry. 33. 4197-4206 (1994)

[文献書誌] Yoshida et al.: "Trichostatin A and trapoxin:novel chemical probes for the role of histone acetylation in chromatin structure and function." BioEssays. in press. (1995)

[文献書誌] Minami,Y.et al.: "Signal transduction mediated by the reconstituted IL-2 receptor: evidence for a cell type-specific function of IL-2 receptor B chain." J.Immunol.152. 5680-5690 (1994)

[文献書誌] Kawahara,Y.et al.: "Evidence for a critical role for the cytoplasmic region of the interleukin2 (IL-2) receptor γchain in IL-2,IL-4,and IL-7 signalling." Mol.Cell.Biol.14. 5433-5440 (1994)

[文献書誌] Miyazaki,T.et al.: "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits." Science. 266. 1045-1047 (1994)

[文献書誌] Minami,Y.et al.: "Protein typrosine kinase Syk is associated with and activated by the IL-2 receptor: possible 1ink with the c-myc induction pathway." Immunity. 2. 89-100 (1995)

[文献書誌] Minami,Y.et al.: "The IL-2 signalling; recruitment and activation of multiple protein tyrosin kinases by the IL-2 receptor components." Curr.Op.Cell Biol.(in press). (199)

[文献書誌] 宮川都吉ら (編・著): "酵母に見る最新の真核生物像 酵母実験系への誘い 担当部分:酵母のストレス応答とカルシニューリン" 東江の編, 共立出版, 489 (1994)

[文献書誌] Takai,Y.,et al.: "Proceedings of 24th International Symposium of the Princess Takamatsu Cancer Research Fund,Molecular and cellular basis for cell to cell interactions; its significance in cancer" Princeton Scientific Publishing Co.,Inc.,Princeton,U.S.A., (1994)

[文献書誌] Takai,Y.,et al.: "Molecular Nerobiology; Mecahnism Common to Brain,Skin,and Immune System" John Willy & Sons,Inc.,Toronto, 247 (1994)

1994 年度実績報告書

東江昭夫東京大学, 大学院・理学系研究科, 教授 (90029249)

[文献書誌] 宮川都吉ら (編・著): "酵母に見る最新の真核生物像酵母実験系への誘い担当部分:酵母のストレス応答とカルシニューリン" 東江の編, 共立出版, 489 (1994)