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Molecular Mechanisms of Differentiation and Proliferation Switches

Research Project

Project/Area Number 05269102
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionNational Institute of Genetics (1994-1995)
Kyoto University (1993)

Principal Investigator

KATSURA Isao (1994-1996)  Natl.Inst.Genetics, Struct.Biol.Cent., Professor, 遺伝情報研究センター, 教授 (00107690)

登田 隆 (1993)  京都大学, 理学部, 講師 (50197894)

Co-Investigator(Kenkyū-buntansha) MASUI Tohru  Natl.Inst.Health Sci., 3rd Dept.Mut.Res., Senior Researcher, 変異研究部第3室, 主任研究官 (50150082)
SUGIMOTO Katsunori  Nagoya Univ., Faculty of Science, Research Associate, 理学部, 助手 (90192616)
NAKABEPPU Yusaku  Kyushu Univ., Med.Inst.Bioreg., Research Associate, 生体防御医学研究所, 助手 (30180350)
INAGAKI Masaki  Tokyo Metr.Inst.Gerontol., Dept.Neurophysiol., Dept.Head, 神経生理部門, 部門長 (30183007)
NISHIDA Eisuke  Kyoto Univ., Inst.for Virus Res., Professor, ウイルス研究所, 教授 (60143369)
古市 貞一  東京大学, 医科学研究所, 助教授 (50219094)
桂 勲  国立遺伝学研究所, 情報研究センター, 教授 (00107690)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥116,000,000 (Direct Cost: ¥116,000,000)
Fiscal Year 1995: ¥40,000,000 (Direct Cost: ¥40,000,000)
Fiscal Year 1994: ¥44,000,000 (Direct Cost: ¥44,000,000)
Fiscal Year 1993: ¥32,000,000 (Direct Cost: ¥32,000,000)
Keywordscell cycle / cell differentiation / cell proliferation / cyclin / cdk / phosphorylation / protein kinase / control mechanism / シグナル伝達 / 細胞増殖制御 / プロテインキナーゼ / プロテインフォスファターゼ / 転写因子
Research Abstract

Research on the control mechanisms of cell-proliferation and cell-differentiation was performed from the viewpoint of cell-cycle, and the following results were obtained. (1) C.elegans hch-1 gene, which controls hatching and cell-migration, encodes a protein related to BMP-1 and TOLLOID (Katsura). (2) The MAPKK/MAPK cascade is necessary and sufficient for the initiation of Xenopus oocyte maturation (Nishida). (3) Cdc2 kinase, Ckinase and CF kinase were shown to phosphorylate intermediate filament proteins during the cell cycle, by using phosphoprotein-specific antibodies (Inagaki). (4) Expression of DELTAFosB in quiescent cells initiates cell proliferation through increase of cyclin E and CDK2 mRNAs by decrease of their degradation rate (Nakabeppu). (5) Replication factor C is involved in the S phase check-point control, because a ts mutation in its subunit gene RFC5 is suppressed by the overproduction of SPK1/Rad53 kinase (Sugimoto). (6) epi-1, a gene specific for the growth arrest of human epithelial cells, resembles warts/large tumor suppressor, a Drosophila tumor suppressor gene (Masui). (7) Human cDNAs of a new TGF-beta receptor subtype, a 14-4-3 protein and a novel protein HCP1, enhance the transcription of inositol-synthesizing enzymes in yeast cells (Nikawa). The results obtained by diverse materials and methods revealed the basic and species-specific mechanisms of the switches in cell-proliferation/differentiation.

Report

(4 results)
  • 1996 Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] R.Hishida et al.: "hch-l,a gene required for normal hatching and normal migration of a neuroblast in C.elegans,encodes a protein related to TOLLOID and BMP-1." The EMBO Journal. 15. 4111-4122 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Gotoh et al.: "Involvement of the MAP kinase kascade in Xenopus mesoderm induction." The EMBO Journal. 14. 2491-2498 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Sekimata et al.: "Detection of protein kinase activity specifically activated at metaphase-anaphase transition." Journal of Cell Biology. 132. 635-641 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Oda et al.: "Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells emerging from the G0 state." Oncogene. 10. 1341-1351 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Sugimoto et al.: "Rfc5,a small subunit of replication factor C complex,couples DNA replication and mitosis in budding yeast." Proc.Natl.Acad.Sci.USA. 93. 7048-7052 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Masui: "Establishment of an outgrowth culture system to study growth regulation of normal human epithelium." In Vitro Cell.Dev.Biol.-Animal. 31. 440-446 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Hisamoto et al.: "The EGP1 gene may be a positive regulator of protein phosphatase type 1 in the growth control of Saccharomyces cerevisiae." Mol.Cell.Biol.15. 3767-3776 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Shiina et al.: "Microtubule severing by elongation factor-1" Science. 266. 282-285 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Kosako et al.: "Requirement for the MAP kinase kinase/Map kinase cascade in Xenopus oocyte maturation" EMBO J.13. 2131-2138 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tsujimura et al.: "Visualization and function of vimentin phosphorylation by cdc2 kinase during mitosis" J.Biol.Chem.116. 426-434 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Inagaki et al.: "Spatiotemporal distribution of protein kinase and phosphatase activities" Trends Biochem.Sci.19. 448-452 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] B.T.Hope et al.: "Induction of a long-lasting AP-1 complex composed of altered fos-like proteins in brainby chronic cocaine and other chronic treatments" Neuron. 13. 1235-1244 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Nikawa et al.: "Structural and functional conservation of human and yeast HCP genes which can suppress the growth defect of Saccharomyces cerevisiae ire15 mutant." Gene. 171. 107-111 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Katsura et al.: "Isolation,characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans" Genetics. 136. 145-154 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Takai et al.: "Mitosis-specific phosphorylation of vimentin by protein kinase C coupled with reorganization of intracellularmembranes." J.Cell Biol.133. 141-149 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Shiina et al.: "Microtubule-severing activity in M phase." Trends Cell Biol.5. 283-286 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Chen et al.: "Regulation of DFosB and FosB-like proteins by electroconvulsive seizure(ECS)and cocaine treatments." Mol.Pharmacol.48. 880-889 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Sugimoto et al.: "HYS2,an essential gene required for DNA replication in Saccharomyces cerevisiae." Nucleic Acids Res.23. 3493-3500 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] R.Hishida et al.: "hch-1, a gene required for normal hatching and normal migration of a neuroblast in C.elegans, encodes a protein related to TOLLOID and BMP-1." EMBO J.15. 4111-4122 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Gotoh et al.: "Involvement of the MAP kinase kascade in Xenopus mesoderm induction." EBMO J.14. 2491-2498 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Sekimata et al.: "Detection of protein kinase activity specifically activated at metaphase-anaphase transition." J.Cell Biol.132. 635-641 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Oda et al.: "Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells emerging from the G0 state." Oncogene. 10. 1341-1351 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Sugimoto et al.: "Rfc5, a small subunit of replication factor C complex, couples DNA replication and mitosis in budding yeast." Proc.Natl.Acad.Sci.USA 93. 7048-7052 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Masui: "Establishment of an outgrowth culture system to study growth regulation of normal human epithelium." In Vitro Cell.Dev.Biol.-Animal 31. 440-446 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Nikawa et al.: "Structural and functional conservation of human and yeast HCP genes which cansuppress the growth defect of Saccharomyces cerevisiae ire15 mutant." Gene. 171. 107-111 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] I.Katsura et al.: "Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans" Genetics. 136. 145-154 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Takai et al.: "Mitosis-specific phosphorylation of vimentin by protein kinase C coupled with reorganization of intracellularmembranes." J.Cell Biol.133. 141-149 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Shiina et al.: "Microtubule-severing activity in M phase." Trends Cell Biol.5. 283-286 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Chen et al.: "Regulation of DFosB and FosB-like proteins by electroconvulsive seizure (ECS) and cocaine treatments." Mol.Pharmacol.48. 880-889 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Sugimoto et al.: "HYS2, an essential gene required for DNA replication in Saccharomyces cerevisiae." Nucleic Acids Res.23. 3493-3500 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Hisamoto et al.: "The EGP1 gene may be a positive regulator of protein phosphatase type 1 in the growth control of Saccharomyces cerevvisiae." Mol.Cell.Biol.15. 3767-3776 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Shiina et al.: "Microtubule severing by elongation factor-1" Science. 266. 282-285 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Kosako et al.: "Requirement for the MAP kinase kinase/Map kinase cascade in Xenopus oocyte maturation" EMBO J.13. 2131-2138 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tsujimura et al.: "Visualization and function of vimentin phosphorylation by cdc2 kinase during mitosis" J.Biol.Chem.116. 426-434 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Inagaki et al.: "Spatiotemporal distribution of protein kinase and phosphatase activities" Trends Biochem.Sci.19. 448-452 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] B.T.Hope et al.: "Induction of a long-lasting AP-1 complex composed of altered fos-like proteins in brainby chronic cocaine and other chronic treatments" Neuron. 13. 1235-1244 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Gotoh et al.: "Involvement of the MAP kinase kascade in Xenopus mesoderm induction." The EMBO Journal. 14. 2491-2498 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Sekimata et al.: "Detection of protein kinase activity specifically activated at metaphase-anaphase transition." Journal of Cell Biology. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Oda et al.: "Stabilization of cyclin E and cdk2 mRNAs at Gl/S transition in Rat-1A cells emerging from the G0 state." Oncogene. 10. 1341-1351 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Sugimoto et al.: "HYS2,an essential gene required for DNA replication in Saccharomyces cerevisiae." Nucleic Acids Research. 23. 3493-3500 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Masui: "Establishment of an outgrowth culture system to study growth regulation of normal human epithelium." In Vitro Cell.Dev.Biol.-Animal. 31. 440-446 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] J.Nikawa et al.: "Cloning and sequence of the SCS2 gene which can suppress the defect of INO1 expression in an inositol auxotrophic mutant of Saccharomyces cerevisiae" Journal of Biochemistry(Tokyo). 118. 39-45 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] I.Katsura et al.: "Isolation,characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans" Genetics. 136. 145-154 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Shiina et al.: "Microtubule severing by elongation factor-la" Science. 266. 282-285 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Kosako et al.: "Requirement for the MAP kinase kinase/Map kinase cascade in Xenopus oocyte maturation" EMBO J.13. 2131-2138 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Tsujimura et al.: "Visualization and function of vimentin phosphorylation by cdc2 kinase during mitosis" J.Biol.Chem.269. 31097-31106 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Inagaki et al.: "Spatiotemporal distribution of protein kinase and phosphatase activities" Trends in Biochem.Sci.19. 448-452 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] B.T.Hope et al: "Induction of a long-lasting AP-1 complex composed of altered fos-like proteins in brainby chronic cocaine and other chronic treatments" Neuron. 13. 1235-1244 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] I.Katsura et al.: "Isolation,characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans" Genetics. 136. 145-154 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Shiina et al.: "Microtubule severing by elongation factor-la" Science. 266. 282-285 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Kosako et al.: "Requirement for the MAP kinase kinase/Map kinase cascade in Xenopus oocyte maturation" EMBO J.13. 2131-2138 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Tsujimura et al: "Visualization and function of vimentin phosphorylation by cdc2 kinase during mitosis" J.Biol.Chem.269. 31097-31106 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Inagaki et al.: "Spatiotemporal distribution of protein kinase and phosphatase activities" Trends in Biochem.Sci.19. 448-452 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] B.T.Hope et al.: "Induction of a long-lasting AP-1 complex composed of altered fos-like proteins in brainby chronic cocaine and other chronic treatments" Neuron. 13. 1235-1244 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Oda et al.: "Stabilization of cyclin E and cdk2 mRNA at G1-S transition in rat-1A cels emergingfrom the G0 state" Oncogene. 10(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Doi et al.: "MSG5,a novel protein phosphatase promotes adaptation to pheromone response in S.cerevisiae" EMBO J.13. 61-70 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] N.Hisamoto et al.: "The Glc7 type 1 protein phosphatase of Saccharomyces cerevisiae is required for cell cycle progression in G2/M" Mol.Cell.Biol.14. 3158-3165 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Fukamachi et al.: "Hepatocyte growth factor region-specifically stimulates gastro-intestinal epithelial growth in primary culture" Biochem.Biophys.Res.Commun.205. 1445-1451 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Masui et al.: "Establishment of an outgrowth culture system to study growth regulation of normal human epithelium" In Vitro Cell.Develop.Biol.(印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takashi Toda: "Two novel protein kinase C-related genes of fission yeast are essential for cell viability and implicated in cell shape control." EMBO J.12. 1987-1995 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takashi Toda: "Isolation and characterization of the fission yeast protein phosphatase gene ppel+involved in cell shape control and mitosis." Mol.Biol.Cell.4. 303-313 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Isao Katsura: "Isolation,Characterization,and Epistasis of Fluoride-resistant Mutants of Caenorhabditis elegans." Genetics. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Isao Katsura: "In Search of New Mutants in Cell-signaling Systems of the Nematode Caenorhabditis elegans." Genetica. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Eisuke Nishida: "Schizosaccharomyces pombe Spkl is a tyrosine-phosphorylated prtein functionally related to Xenopus kinase." Mol.Cell.Biol.13. 6427-6434 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yusaku Nakabeppu: "Proliferative Activation of Quiescent Rat-1A Cells by DFosB." Mol.Cell.Biol.13. 4157-4166 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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