1995 年度実績報告書

細胞増殖のスイッチと生体高次機能の形成制御

研究課題

研究課題/領域番号	05304056
研究機関	(財)癌研究会
研究代表者	小池克郎財団法人癌研究曾, 癌研究所, 部長 (30085625)
研究分担者	長田重一大阪バイオサイエンス研究所, 部長 (70114428) 竹市雅俊京都大学, 理学部, 教授 (00025454) 広川信隆東京大学, 医学部, 教授 (20010085) 岡山博人東京大学, 医学部, 教授 (40111950) 新井賢一東京大学, 医科学研究所, 教授 (00012782)
キーワード	GM-CSF / Fasリガンド / IP_3レセプター / アクチビン / HGFと器官再生 / カドヘリンと細胞接着 / DNA複製関連蛋白質 / 酵母染色体複製開始
研究概要	細胞増殖のスイッチと生体高次機能の形成の研究において、細胞の数の増加、すなわちゲノム複製に至る過程の制御は中心的課題である。本研究では、増殖因子、分化誘導因子や接着因子による細胞増殖のスイッチのON/OFF機構に注目し、この機構が組織器官の形成や再生の制御にどのように関与しているかについて明かにすることを目的とした研究と討論を行ない、下記にまとめた如くの多くの成果をあげた。 1.GM-CSF、Fasリガンドなどの細胞表面受容体への結合に伴う細胞増殖の促進あるいは細胞死を明かにした。とくに、Fasリガンドについては、リンパ球での発現・分泌を新しく見つけた。 2.アクチビンによる内胚葉分化の誘導が新しく見つけられた。HGFにおいては、間葉由来の形態形成促進因子の役割を見つけた。 3.カドヘリンなどの細胞接着因子が上皮形態形成に必須であることを明かにした。 4.神経系の発生分化におけるIP3レセプターのヘテロ四量体構造、神経細胞内の物資輸送にかかわる細胞骨格に結合するモーター分子を明かにした。 5.細胞周期を調節するG2期チェックポイントの蛋白リン酸化酵素について新しい知見を得た。 DNA複製関連遺伝子、DNAポリメラーゼ、プライマーゼやヘリカーゼ遺伝子の発現制御機構について明かにした。 7.ヒト培養細胞および酵母の複製開始点にかかわる複製関連蛋白質を解析し、Cdc7やDNAポリメラーゼαなどに新しい知見を得た。加えて、本研究の大きな目的である研究討論会については、平成7年12月名古屋で行われた日本分子生物学会において、本研究グループが中心となり、シンポジウム「細胞の増殖と高次機能の形成制御」を行いその成果を発表した。外国からも第一線研究者を招き、最先端の話題について討論することが出来、今後の研究方向についての討論も十分に行われた。なお、平成8年度には研究成果の一部について公開シンポジウムを行なうことことを予定している。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Ishida,S.et.al.,: "A direct role of transcription factor E2F in the c-myc gene expression during granulocyte and macrophage-like differentiation of HL60 cells." Cell Growth and Differentiation. 6. 229-237 (1995)
[文献書誌] Watanabe,S.et.al.,: "Characterization of cis-regulatory elements of the c-myc promoter responding to human GM-CSF or mouse interleukin-03 in mouse proB cell line BA/F3 cells expressing human GM-CSF receptor." Molecular Biology of the Cell. 6. 627-636 (1995)
[文献書誌] Tamura,T.et.al.,: "An IRF-1 dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocyte." Nature. 376. 596-599 (1995)
[文献書誌] Yasunage,M.et al.: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." J.Cell Biol.132. 1-9 (1996)
[文献書誌] Igarashi,K.et.al.,: "Activity and expression of murine small Maf family protein MafK." J.Biol.Chem.270. 7615-7624 (1995)
[文献書誌] Enari,M.et.al.,: "Involvement of an ICE-like protease in Fas-mediated apoptosis." Nature. 375. 78-81 (1995)
[文献書誌] Kinodhiys,K.et.al.,: "Effect of activin and lithium on isolated Xenopus animal blastomeres and response alteration at the midblastula transition." Development. 121. 1581-1589 (1995)
[文献書誌] Nakamura,H.et.al.,: "Isolation of Xenopus HGF gene promoter and its functional analysis in embryos and animal caps." Roux's Arch.Dev.Biol.(in press). (1995)
[文献書誌] Nakamura,H.et.al.,: "Molecular cloning of Xenopus HGF cDNA and its expresson studied in Xenopus early embryogenesis." Mech.Develop.49. 121-131 (1995)
[文献書誌] Overduin,M.et.al.,: "Three-dimensional solution structure and calcium interaction of the epithelial cadherin domain responsible for selective adhesion." Science. 267. 386-389 (1995)
[文献書誌] Ando-Akatsuka,Y.et.al.,: "Interspecies diversity of the occludin sequence:cDNA cloning of human,mouse,dogand rat-kangaroo homologues." J.Cell Biol.(in press). (1996)
[文献書誌] Okada,Y.et.al.,: "The neuron specific kinesin superfamily protein KIFIA is a unique monomeric motor for the anterograde axonal transport of synaptie vesicle precursors." Cell. 81. 769-780 (1995)
[文献書誌] Shibuya,M.: "Role of VEGF-Flt receptor system in nomal and tumor angiogenesis." Adv.Cancer Res.67. 281-316 (1995)
[文献書誌] Sekine,Y.,et.al.,: "Idenification and characterization of the linear IS3 molecules generated by staggered breaks." J.Biol.Chem.271. 197-202 (1996)
[文献書誌] Araki,H.,et al.: "Dpb11,involved in S-phase progression and checkpoint control,interacts with DNA polymerase II(ε)in Saccharomyces cerevisiae." Proc.Natl.Acad.Sci.USA. 92. 11791-11795 (1995)
[文献書誌] Mizushima,T.et al.: "Influence of cluster formation of acidic phospholipids on decrease in the affinity for ATP of DnaA protein." J.Biol.Chem.271(in press). (1996)
[文献書誌] Shoji-Kawaguchi,M.et al.: "Selective inhibition of DNA polymerase by phosphatidylinositol." J.Biochem.117. 1095-1099 (1995)
[文献書誌] Matsuda,T.et al.: "DNA repair protein XPA binds replicaton protein A(RPA)." J.Biol.Chem.270. 4152-4157 (1995)
[文献書誌] Yamaguchi M.et al.: "Essential role of E2F recognition site in regulation of the proliferating cell nuclear antigen gene promoter during Drosophila development." J.Biol.Chem.270. 25159-25165 (1995)
[文献書誌] Murakami,H.et al.: "A kinase from fission yeast resposible for blocking mitosis in S phase." Nature. 374. 817-819 (1995)
[文献書誌] Matsumoto,K.et al.: "Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication system containing eukaryotic replication origins." Biochemistry. 34. 7913-7922 (1995)
[文献書誌] Ishimi,Y.et al.: "Synthesis of simian virus 40 C-family catenated dimers in vivo in the presence of ICRF-193." J.Mol.Biol.247. 835-839 (1995)
[文献書誌] Nagai,Y.et al.: "Ubiquitin-activating enzyme,E1,is phosphorylated in mammalian cells by the protein kinase CDC2." J.Cell Sci.108. 2145-2152 (1995)
[文献書誌] Masai,H.et al.: "hsk1+,a Schizosaccharomyces Pombe gene related to Saccharomyces cerevisiae CDC7 kinase,is required for chromosomal replication." EMBO J.14. 3094-3104 (1995)
[文献書誌] Matsumoto,M.et al.: "Ataxia and epileptic seizures in mice lacking type i inositol 1,4,5-trisphosphate receptor." Nature. 379. 168-171 (1996)
[文献書誌] Toyama-Sorimachi,N.et al.: "A novel ligand for CD44 is serglycin,a hematopoietic cell lineage-specific proteoglycan." J.Biol.Chem.270. 7437-7444 (1995)

1995 年度 実績報告書

細胞増殖のスイッチと生体高次機能の形成制御

研究代表者

小池 克郎 財団法人癌研究曾, 癌研究所, 部長 (30085625)

研究成果

[文献書誌] Ishida,S.et.al.,: "A direct role of transcription factor E2F in the c-myc gene expression during granulocyte and macrophage-like differentiation of HL60 cells." Cell Growth and Differentiation. 6. 229-237 (1995)

[文献書誌] Watanabe,S.et.al.,: "Characterization of cis-regulatory elements of the c-myc promoter responding to human GM-CSF or mouse interleukin-03 in mouse proB cell line BA/F3 cells expressing human GM-CSF receptor." Molecular Biology of the Cell. 6. 627-636 (1995)

[文献書誌] Tamura,T.et.al.,: "An IRF-1 dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocyte." Nature. 376. 596-599 (1995)

[文献書誌] Yasunage,M.et al.: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." J.Cell Biol.132. 1-9 (1996)

[文献書誌] Igarashi,K.et.al.,: "Activity and expression of murine small Maf family protein MafK." J.Biol.Chem.270. 7615-7624 (1995)

[文献書誌] Enari,M.et.al.,: "Involvement of an ICE-like protease in Fas-mediated apoptosis." Nature. 375. 78-81 (1995)

[文献書誌] Kinodhiys,K.et.al.,: "Effect of activin and lithium on isolated Xenopus animal blastomeres and response alteration at the midblastula transition." Development. 121. 1581-1589 (1995)

[文献書誌] Nakamura,H.et.al.,: "Isolation of Xenopus HGF gene promoter and its functional analysis in embryos and animal caps." Roux's Arch.Dev.Biol.(in press). (1995)

[文献書誌] Nakamura,H.et.al.,: "Molecular cloning of Xenopus HGF cDNA and its expresson studied in Xenopus early embryogenesis." Mech.Develop.49. 121-131 (1995)

[文献書誌] Overduin,M.et.al.,: "Three-dimensional solution structure and calcium interaction of the epithelial cadherin domain responsible for selective adhesion." Science. 267. 386-389 (1995)

[文献書誌] Ando-Akatsuka,Y.et.al.,: "Interspecies diversity of the occludin sequence:cDNA cloning of human,mouse,dogand rat-kangaroo homologues." J.Cell Biol.(in press). (1996)

[文献書誌] Okada,Y.et.al.,: "The neuron specific kinesin superfamily protein KIFIA is a unique monomeric motor for the anterograde axonal transport of synaptie vesicle precursors." Cell. 81. 769-780 (1995)

[文献書誌] Shibuya,M.: "Role of VEGF-Flt receptor system in nomal and tumor angiogenesis." Adv.Cancer Res.67. 281-316 (1995)

[文献書誌] Sekine,Y.,et.al.,: "Idenification and characterization of the linear IS3 molecules generated by staggered breaks." J.Biol.Chem.271. 197-202 (1996)

[文献書誌] Araki,H.,et al.: "Dpb11,involved in S-phase progression and checkpoint control,interacts with DNA polymerase II(ε)in Saccharomyces cerevisiae." Proc.Natl.Acad.Sci.USA. 92. 11791-11795 (1995)

[文献書誌] Mizushima,T.et al.: "Influence of cluster formation of acidic phospholipids on decrease in the affinity for ATP of DnaA protein." J.Biol.Chem.271(in press). (1996)

[文献書誌] Shoji-Kawaguchi,M.et al.: "Selective inhibition of DNA polymerase by phosphatidylinositol." J.Biochem.117. 1095-1099 (1995)

[文献書誌] Matsuda,T.et al.: "DNA repair protein XPA binds replicaton protein A(RPA)." J.Biol.Chem.270. 4152-4157 (1995)

[文献書誌] Yamaguchi M.et al.: "Essential role of E2F recognition site in regulation of the proliferating cell nuclear antigen gene promoter during Drosophila development." J.Biol.Chem.270. 25159-25165 (1995)

[文献書誌] Murakami,H.et al.: "A kinase from fission yeast resposible for blocking mitosis in S phase." Nature. 374. 817-819 (1995)

[文献書誌] Matsumoto,K.et al.: "Stimulation of DNA synthesis by mouse DNA helicase B in a DNA replication system containing eukaryotic replication origins." Biochemistry. 34. 7913-7922 (1995)

[文献書誌] Ishimi,Y.et al.: "Synthesis of simian virus 40 C-family catenated dimers in vivo in the presence of ICRF-193." J.Mol.Biol.247. 835-839 (1995)

[文献書誌] Nagai,Y.et al.: "Ubiquitin-activating enzyme,E1,is phosphorylated in mammalian cells by the protein kinase CDC2." J.Cell Sci.108. 2145-2152 (1995)

[文献書誌] Masai,H.et al.: "hsk1+,a Schizosaccharomyces Pombe gene related to Saccharomyces cerevisiae CDC7 kinase,is required for chromosomal replication." EMBO J.14. 3094-3104 (1995)

[文献書誌] Matsumoto,M.et al.: "Ataxia and epileptic seizures in mice lacking type i inositol 1,4,5-trisphosphate receptor." Nature. 379. 168-171 (1996)

[文献書誌] Toyama-Sorimachi,N.et al.: "A novel ligand for CD44 is serglycin,a hematopoietic cell lineage-specific proteoglycan." J.Biol.Chem.270. 7437-7444 (1995)

1995 年度実績報告書

小池克郎財団法人癌研究曾, 癌研究所, 部長 (30085625)