1994 Fiscal Year Annual Research Report

細胞増殖のスイッチと生体高次機能の形成制御

Research Project

Project/Area Number	05304056
Research Institution	Japanese Foundation For Cancer Research
Principal Investigator	小池克郎財団法人癌研究會, 癌研究所, 部長 (30085625)
Co-Investigator(Kenkyū-buntansha)	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) 浅島誠東京大学, 教養学部, 教授 (00090564) 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)
Keywords	IL3 / Fasリガンド / IP3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複製関連遺伝子 / 酵母複製開始点
Research Abstract	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、細胞の増殖因子、分化誘導因子や接着因子によるゲノム複製のスイッチのON/OFF機構を明かにし、このスイッチ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を行ない、下記の多くの成果をあげた。 1.IL3、INF-β、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抑制や細胞死を明かにし、シグナル伝達に必要な受容体中のドメイン構造を明かにした。 2.アクチビンやHGFホモログによる中胚葉組織の誘導やHGFによる肝再生のメカニズムを明かにした。 3.CD44やカテニン、カドヘリン発現による細胞接着と細胞増殖変化を明かにした。 4.神経系の発生分化におけるIP3レセプターや、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CDk4キナーゼ遺伝子とG2期チェックポイント遺伝子について新しい知見を得た。 6.DNA複製関連遺伝子、とくに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解析した。 7.ヒト培養細胞および酵母複製開始点について複製起点に結合する蛋白質などを解析し、in vitroDNA合成系の開発を試みた。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、10月29日に東京で細胞増殖とシグナル伝達関連遺伝子の研究グループが中心となり、成果と今後の研究方向について議論した。平成7年1月23日には研究成果の一部について公開シンポジウム「細胞増殖のスイッチと生体高次機能の形成制御」を東京大学山上会館(本郷)で行ない非常に成果をあげることが出来た。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Koike,K.et.al.,: "Receptor-mediated gene transfer into hepatic cells using asialoglycoprotein-labeled liposomes." "Gene Therapy for Neoplastic Diseases"Annals of the New. 716. 331-333 (1994)
[Publications] Masai,H.et.al.,: "Replication and transcription on single-stranded DNA templates:proteins that specificaly recognize single-stranded DNA sequences with a higher order structure." Mole.Biol.(Life Sci.Adv.). 13. 19-37 (1994)
[Publications] Takahashi,T.et.al.,: "Generalized lymphoproliferative disease in mice,caused by a point mutation in the Fas ligand." Cell. 76. 969-976 (1994)
[Publications] Nagata,S.: "Apoptosis-mediating Fas antigen and its natural mutation.in"Apoptosis II,The molecular basis of cell death"" Cold Spring Harbor Laboratory Press. 313-326 (1994)
[Publications] Mizuno,K.et.al.,: "Hairpin loop and second kringle-domain are essential sites for heparin-binding and biological activity of hepatocyte growth factor." J.Biol.Chem.269. 1131-1136 (1994)
[Publications] Watabe,M.et.al.,: "Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a despersed carcinoma line." J.Cell Biol.127. 247-256 (1994)
[Publications] Tsukita,Sa.et.al.,: "EMR family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons" J.Cell.Biol.126. 391-401 (1994)
[Publications] Nakada,S.et.al.,: "Cyclic AMP-dependent phospholylation of an immunoaffinity purified type I homotetrameric inositol 1,4,5-trisphosphate receptor increases Ca_<2+> flux in" J.Biol.chem.296. 6735-6742 (1994)
[Publications] Obara-Ishihara,T.et.al.,: "A B-type cyclin regulates conjugation via interaction with cel cycle 'start'genes in fission yeast." EMBOJ.13. 1863-1872 (1994)
[Publications] Gotoh,N.et.al.,: "Epidermal growth factor receptor-mutant lacking the autophosphorylation sites induces phosphorylation of Shc and association of Shc with Grb2/Ash,and retains mitogenic activity." Proc.Natl.Acad.Sci.USA. 91. 167-171 (1994)
[Publications] Ishimi,Y.et.al.,: "DNA replication from initiation zones of mammalian cells in a model system." Mol.Cell.Biol.14. 6489-6496 (1994)
[Publications] Matsutani,C.et.al.,: "Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23." EMBOJ.13. 1831-1843 (1994)
[Publications] Fukai,A.et.al.,: "Identification of activins A,AB and B and follistatin proteins in the xenopus embryos." Devlo.Biol.163. 278-280 (1994)
[Publications] Era,T.et.al.,: "How B precursor cells are driven to cycle." Immunol.Rev.137. 36-51 (1994)

1994 Fiscal Year Annual Research Report

細胞増殖のスイッチと生体高次機能の形成制御

Principal Investigator

小池 克郎 財団法人 癌研究會, 癌研究所, 部長 (30085625)

Research Products

[Publications] Koike,K.et.al.,: "Receptor-mediated gene transfer into hepatic cells using asialoglycoprotein-labeled liposomes." "Gene Therapy for Neoplastic Diseases"Annals of the New. 716. 331-333 (1994)

[Publications] Masai,H.et.al.,: "Replication and transcription on single-stranded DNA templates:proteins that specificaly recognize single-stranded DNA sequences with a higher order structure." Mole.Biol.(Life Sci.Adv.). 13. 19-37 (1994)

[Publications] Takahashi,T.et.al.,: "Generalized lymphoproliferative disease in mice,caused by a point mutation in the Fas ligand." Cell. 76. 969-976 (1994)

[Publications] Nagata,S.: "Apoptosis-mediating Fas antigen and its natural mutation.in"Apoptosis II,The molecular basis of cell death"" Cold Spring Harbor Laboratory Press. 313-326 (1994)

[Publications] Mizuno,K.et.al.,: "Hairpin loop and second kringle-domain are essential sites for heparin-binding and biological activity of hepatocyte growth factor." J.Biol.Chem.269. 1131-1136 (1994)

[Publications] Watabe,M.et.al.,: "Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a despersed carcinoma line." J.Cell Biol.127. 247-256 (1994)

[Publications] Tsukita,Sa.et.al.,: "EMR family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons" J.Cell.Biol.126. 391-401 (1994)

[Publications] Nakada,S.et.al.,: "Cyclic AMP-dependent phospholylation of an immunoaffinity purified type I homotetrameric inositol 1,4,5-trisphosphate receptor increases Ca_<2+> flux in" J.Biol.chem.296. 6735-6742 (1994)

[Publications] Obara-Ishihara,T.et.al.,: "A B-type cyclin regulates conjugation via interaction with cel cycle 'start'genes in fission yeast." EMBOJ.13. 1863-1872 (1994)

[Publications] Gotoh,N.et.al.,: "Epidermal growth factor receptor-mutant lacking the autophosphorylation sites induces phosphorylation of Shc and association of Shc with Grb2/Ash,and retains mitogenic activity." Proc.Natl.Acad.Sci.USA. 91. 167-171 (1994)

[Publications] Ishimi,Y.et.al.,: "DNA replication from initiation zones of mammalian cells in a model system." Mol.Cell.Biol.14. 6489-6496 (1994)

[Publications] Matsutani,C.et.al.,: "Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23." EMBOJ.13. 1831-1843 (1994)

[Publications] Fukai,A.et.al.,: "Identification of activins A,AB and B and follistatin proteins in the xenopus embryos." Devlo.Biol.163. 278-280 (1994)

[Publications] Era,T.et.al.,: "How B precursor cells are driven to cycle." Immunol.Rev.137. 36-51 (1994)

小池克郎財団法人癌研究會, 癌研究所, 部長 (30085625)