1993 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	サイトカイン / 細胞表面受容体 / 細胞死 / アクチビン / HGFと肝再生 / 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DNA合成スイッチの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、下記にまとめる様な多くの成果をあげた。 1.サイトカインの細胞表面受容体への結合に伴う細胞DNA合成や細胞死を明かにし、結合に必要な受容体のドメイン構造を明かにした。 2.アクチビン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.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細胞間認識を仲介する分子や、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キナーゼ遺伝子とその機能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単離に成功した。 7.ヒト培養細胞および酵母複製開始点についてin vitro DNA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、8月25日に大阪で複製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。12月16日には研究班全体の討論会を幕張で行ない、異なった分野の研究者の相互理解を大いに深めた。平成6年2月28日には研究成果の一部について公開シンポジウム(「細胞への刺激と遺伝子の応答」)を東京KDDホールで行ない非常に成果をあげることが出来た。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] Ishida,S.et al.,: "Transcription from the P2 promoter of huma prot-oncogene myc iis suppressed by retinoic acid through an interaction between the E2F element and its binding protein." Cell Growth&Diff.5,in press. (1994)
[Publications] Takada,S.et.al.,: "Interaction of hepatitis B virus X protein with a serine protease tryptase TL2,as an inhibitor." Oncogene. 9. 341-348 (1994)
[Publications] Kondo,M.et al.,: "Sharing of a interleukin-2(IL-2)receptor gamma chain between receptor for IL-2 and IL-4." Science. 62. 1874-1877 (1993)
[Publications] Sato,N.et.al.,: "A signal transduction by the high affinity GM-CSF rceptor:two distinct cytoplasic regions of the common B subunit responsible for defferent signaling" EMBOJ.12. 4181-4189 (1993)
[Publications] Koyano-Nakagawa,N.et.al.: "Molecutar cloning of a novel human cDNA encoding a zinc finger protein that binds to the interlwukin 3 promoter" Mol.Cell.Biol.in press. (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] Kawaida,K.et.al.: "Hepatocyte growth factor prevent acute renal failure and accelerate renal regeneration." Proc.Natl.Acad.Sci.USA. in press.(1994)
[Publications] Itho,N.and Nagata,S.: "A novel protein doain required for apoptosis:mutational analysis of human Fas antigen." J.Biol.Chem.268. 10932-10937 (1993)
[Publications] Hirokawa,N.: "Microtubule organization and dynamics dependent on microtubule-associated proteins." Current Opinion in Cell Biology. 6. 74-82 (1994)
[Publications] Harada,A.et.al.: "Tau is not essential for polarized neuronal cell morphogenesis but important for microtubule organization and stabilization in small caliber axons." Nature. in press. (1994)
[Publications] Matsuzaki,Y.et.al.: "Chatacterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation." J.Xep.Med.178. 9125-9129 (1993)
[Publications] Kondo,M.et.al.: "Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes" Science. in press. (1994)
[Publications] Jinnno,S.et.al.: "Cdc25A is a novel phosphatase functioning early in the cell cycle." EMBOJ.13,in press. (1994)
[Publications] Rosenet,O.et.al.: "Close physical linkage of the FLT1 and FLT3 genes on chromosome 13 in man and chromosome 5 in mouse." Oncogene. 8. 173-179 (1993)
[Publications] Jinnno,A.et.al.,: "Testis-specific mak protein kinase is expressed specifically in the meiotic phase in spermatogenesis and is specifically in the meiotic phase in spermatogenesis and is associated" Mol.Cell.Biol.13. 4146-4156 (1993)
[Publications] Segawa,K.et.al.: "Abrogation of p53-mediated transactivation by SV40 large T antigen" Oncogene. 8. 543-548 (1993)
[Publications] Matsumoto,K.et.al.: "TAF-1,a novel host factor required to stimulate the adenovirus core DNA replication" J.Biol.Chem.268. 10582-10587 (1993)
[Publications] Yamao,F.et.al.: "Conditional resistance to thymineless death predominatly selects DNA synthesis-deficient mutants of mammalian cells." Mutation Reseatch. 289. 83-89 (1993)
[Publications] Fujii,G.et.al.: "Molecular cloning of cDNAs for two Xenopus proteasome subunits and their expression in adult tissues" Biochim.Biophys.Acta. 1216. 65-72 (1993)
[Publications] Okuhara,K.et.al.: "Initiation of DNA synthesis in a high molecular weight fraction of Xenopus egg extract." Cell Biol.Intern. 17. 275-282 (1993)
[Publications] Hamaguchi,M.et.al.: "p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system." EMBOJ.12. 307-314 (1993)
[Publications] Takeuchi,M.et.al.,: "Cytoplasmic control of cadherin-mediated cell-cell adhesion." Cold Spring Harbor Quant.Biol.LV. 327-334 (1993)
[Publications] Toyama-Sorimachi,N.et.: "A novel ligand for CD44 sulfated proteoglycan." Int.Immunol.in press. (1994)
[Publications] Sugiyama,A.et.al.: "A zinc finger protein controls the onset of premeiotic DNA synthesis of fission year in a Mei2 independent cascade" EMBOJ.13,in press. (1994)
[Publications] Ohashi,K.et.al.,: "Cloning novel receptor tyrosine kinase Sky,predominantly expressed in brain." Oncogene. 9. 699-705 (1994)
[Publications] Matsuzaki,Y.et.al.: "Characterization of c-kit positive intrathymic stem cells that are restricted to lumphoid differentiation." J.Exp.Med.178. 1283-1292 (1993)
[Publications] Suda,T.et.al.,: "Molecular cloning and expression of the Fas ligand,a novel member of the tumor necrosis factor family" Cell. 75. 1169-1178 (1993)
[Publications] Takahashi,T.et.al.,: "Generalized lymphoproliferative desease (gld) in mice caused by a point mutation in the Fas ligand." Cell. in press (1994)
[Publications] Moriya,N.et.al.: "Induction of renal tubes by activin and retinoic acid in Xenopus ectoderm." Develop.Growth Differe.35. 123-128 (1993)
[Publications] Fukui,A.et.al.: "Isolation and characterization of Xenopusfollistatin and activins." Developmental Biol.159. 134-139 (1993)

1993 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] Ishida,S.et al.,: "Transcription from the P2 promoter of huma prot-oncogene myc iis suppressed by retinoic acid through an interaction between the E2F element and its binding protein." Cell Growth&Diff.5,in press. (1994)

[Publications] Takada,S.et.al.,: "Interaction of hepatitis B virus X protein with a serine protease tryptase TL2,as an inhibitor." Oncogene. 9. 341-348 (1994)

[Publications] Kondo,M.et al.,: "Sharing of a interleukin-2(IL-2)receptor gamma chain between receptor for IL-2 and IL-4." Science. 62. 1874-1877 (1993)

[Publications] Sato,N.et.al.,: "A signal transduction by the high affinity GM-CSF rceptor:two distinct cytoplasic regions of the common B subunit responsible for defferent signaling" EMBOJ.12. 4181-4189 (1993)

[Publications] Koyano-Nakagawa,N.et.al.: "Molecutar cloning of a novel human cDNA encoding a zinc finger protein that binds to the interlwukin 3 promoter" Mol.Cell.Biol.in press. (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] Kawaida,K.et.al.: "Hepatocyte growth factor prevent acute renal failure and accelerate renal regeneration." Proc.Natl.Acad.Sci.USA. in press.(1994)

[Publications] Itho,N.and Nagata,S.: "A novel protein doain required for apoptosis:mutational analysis of human Fas antigen." J.Biol.Chem.268. 10932-10937 (1993)

[Publications] Hirokawa,N.: "Microtubule organization and dynamics dependent on microtubule-associated proteins." Current Opinion in Cell Biology. 6. 74-82 (1994)

[Publications] Harada,A.et.al.: "Tau is not essential for polarized neuronal cell morphogenesis but important for microtubule organization and stabilization in small caliber axons." Nature. in press. (1994)

[Publications] Matsuzaki,Y.et.al.: "Chatacterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation." J.Xep.Med.178. 9125-9129 (1993)

[Publications] Kondo,M.et.al.: "Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes" Science. in press. (1994)

[Publications] Jinnno,S.et.al.: "Cdc25A is a novel phosphatase functioning early in the cell cycle." EMBOJ.13,in press. (1994)

[Publications] Rosenet,O.et.al.: "Close physical linkage of the FLT1 and FLT3 genes on chromosome 13 in man and chromosome 5 in mouse." Oncogene. 8. 173-179 (1993)

[Publications] Jinnno,A.et.al.,: "Testis-specific mak protein kinase is expressed specifically in the meiotic phase in spermatogenesis and is specifically in the meiotic phase in spermatogenesis and is associated" Mol.Cell.Biol.13. 4146-4156 (1993)

[Publications] Segawa,K.et.al.: "Abrogation of p53-mediated transactivation by SV40 large T antigen" Oncogene. 8. 543-548 (1993)

[Publications] Matsumoto,K.et.al.: "TAF-1,a novel host factor required to stimulate the adenovirus core DNA replication" J.Biol.Chem.268. 10582-10587 (1993)

[Publications] Yamao,F.et.al.: "Conditional resistance to thymineless death predominatly selects DNA synthesis-deficient mutants of mammalian cells." Mutation Reseatch. 289. 83-89 (1993)

[Publications] Fujii,G.et.al.: "Molecular cloning of cDNAs for two Xenopus proteasome subunits and their expression in adult tissues" Biochim.Biophys.Acta. 1216. 65-72 (1993)

[Publications] Okuhara,K.et.al.: "Initiation of DNA synthesis in a high molecular weight fraction of Xenopus egg extract." Cell Biol.Intern. 17. 275-282 (1993)

[Publications] Hamaguchi,M.et.al.: "p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system." EMBOJ.12. 307-314 (1993)

[Publications] Takeuchi,M.et.al.,: "Cytoplasmic control of cadherin-mediated cell-cell adhesion." Cold Spring Harbor Quant.Biol.LV. 327-334 (1993)

[Publications] Toyama-Sorimachi,N.et.: "A novel ligand for CD44 sulfated proteoglycan." Int.Immunol.in press. (1994)

[Publications] Sugiyama,A.et.al.: "A zinc finger protein controls the onset of premeiotic DNA synthesis of fission year in a Mei2 independent cascade" EMBOJ.13,in press. (1994)

[Publications] Ohashi,K.et.al.,: "Cloning novel receptor tyrosine kinase Sky,predominantly expressed in brain." Oncogene. 9. 699-705 (1994)

[Publications] Matsuzaki,Y.et.al.: "Characterization of c-kit positive intrathymic stem cells that are restricted to lumphoid differentiation." J.Exp.Med.178. 1283-1292 (1993)

[Publications] Suda,T.et.al.,: "Molecular cloning and expression of the Fas ligand,a novel member of the tumor necrosis factor family" Cell. 75. 1169-1178 (1993)

[Publications] Takahashi,T.et.al.,: "Generalized lymphoproliferative desease (gld) in mice caused by a point mutation in the Fas ligand." Cell. in press (1994)

[Publications] Moriya,N.et.al.: "Induction of renal tubes by activin and retinoic acid in Xenopus ectoderm." Develop.Growth Differe.35. 123-128 (1993)

[Publications] Fukui,A.et.al.: "Isolation and characterization of Xenopusfollistatin and activins." Developmental Biol.159. 134-139 (1993)

小池克郎財団法人癌研究會, 癌研究所, 部長 (30085625)