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Regulation of cell-cycle movement and cell transformation by nuclear oncogenes.

Research Project

Project/Area Number 10470477
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

ARIGA Hiroyoshi  Hokkaido Univ., Grad. School of Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (20143505)

Co-Investigator(Kenkyū-buntansha) KITAURA Hirotake  Hokkaido Univ., Grad. School of Pharm. Sci., Res. Associate, 大学院・薬学研究科, 助手 (10281817)
TAIRA Takahiro  Hokkaido Univ., Grad. School of Pharm. Sci., Asso. Prof., 大学院・薬学研究科, 助教授 (70197036)
ARIGA Sanae  Hokkaido Univ., Grad. School of Pharm. Sci., Prof., 医療技術短期大学部, 教授 (90184283)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordsc-myc / PRC1 / tumor suppresser / transcrition / cell cycle / apoptosis / phosphorylation / chromatin / Pim-1
Research Abstract

We have identified several c-Myc binding proteins whose functions would modify or regulate the versatile functions of c-Myc. Proteins we identified are AMY-1, MM-1, MSSP, CBF/NF-Y, ORC1, CDC6 and cdk inhibitor p21. AMY-1, MM-1 and MSSP are novel proteins and their cDNAS were cloned. These proteins were classified to the categories including factors for transcription (AMY-1, MM-1 and CBF/NF-Y), DNA replication (MSSP, ORC1 and CDC6) and cell-cycle movement (p21). In terms of transcription function of c-Myc, AMY-1 acted as a positive factor and the others were as negative factors. Especially MM-1 has a character for a putative tumor suppresser; the substitution of amino acid from alanine to arginine at a position of 157 of MM-1 was quite frequently occurred in cells derived from both cultured cells and cancer patient tissues of lymphoma, leukemia and tong cancer. This arginine mutation abrogated the negative effects of MM-1 on c-Myc.
In addition to c-Myc-related function of AMY-1, AMY-1 was found to contain the dynamic function affecting A-kinase and actin polymerization. AMY-1 bound to AKAP84 and its alternative splicing variant, AKAP149, both of which anchored A-kinase to the respective cell location. After AMY-1 bound to AKAP84, A-kinase complex turned to move on the surface of mitochondria of sperm and worked for sperm mobilization. AMY-1 bound to AKAP149 made the actin be polymerized on the mitochondria around nucle. These structural different organization of actin filaments may tend to the tumor formation.
Null-mutation of MSSP tended to be lethal during developmental stage. These finding altogether suggest that c-Myc binding proteins play roles at crucial steps of cell maturation, fertilization in addition to the modulation to c-Myc functions.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Taira T.: "Cell cycle-dependent switch of up-and down-regulation of himan hsp70 gene expression by interaction between c-Myc and CBF/NF-Y"J.Biol.Chem.. 274. 24270-24279 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Niki T.: "NSSP promotes the ras/myc cooperative cell transforming activity by binding to C-MYC"Genes Cells. 5. 127-140 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitaura H.: "Reciprocal regulation via protein-protein interaction between c-Myc and p21cip1/waf1/sdi1 in DNA replication and transcription"J.Biol.Chem.. 275(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kyo S.: "Sp1 cooperates with c-Myc to activate transcription of human telomerase reverse transcriptase (hTERT) gene"Nucleic Acids Res.. 28. 339-345 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koike N.: "Identification of heterochromatin protein 1 (HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional"FEBS Lett.. 467. 17-21 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujimoto M.: "Structure and comparison of genomic and complementary DNAs of mouse MSSP, a c-Myc binding protein"Int.J.Onc.. 16. 245-251 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Taira, T., Sawai, M., Ikeda, M., Tamai, K., Iguchi-Ariga. S.M.M. and Ariga, H.: "Cell cycle-dependent switch of up- and down-regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y."J. Biol. Chem.. 274. 24270-24279 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Niki, T., Izumi, S., Saegusa, Y., Taira, T., Takai, T., Iguchi-Ariga, S.M.M., and Ariga, H.: "MSSP promotes the ras/myc cooperative cell transforming activity by binding to C-MYC."Genes Cells. 5. 127-140 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitaura, H., Shinshi, M., Uchikoshi, Y., Ono, T., Tsurimoto, T., Yoshikawa, H., Iguchi-Ariga, S.M. M. and Ariga, H.: "Reciprocal regulation via protein-protein interaction between c-Myc andp21cip1/waf1/sdi1 in DNA replication and transcription."J. Biol. Chem.. 275(in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kyo, S., Takakura, M., Taira, T., Kanaya, T., Itoh, H., Yutsudo, M., Ariga, H. and Inoue, M.: "Sp1 cooperates with c-Myc to activate transcription of human telomerase reverse transcriptase (hTERT) gene."Nucleic Acids Res.. 28. 669-677 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koike, N., Maita, H., Taira, T., Ariga, H. and Iguchi-Ariga, S.M.M.: "Identification of heterochromatin protein 1 (HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional repression function of HP1."FEBS Lett.. 467. 17-21 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Fujimoto, M., Matsumoto, K., Iguchi-Ariga, S.M.M and Ariga, H.: "Structure and comparison of genomic a complementary DNAs of mouse MSSP, a c-Myc binding protein."Int. J. Onc.. 16. 245-251 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Taira, T.: "Cell cycle-dependent switch of up- and down -regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y"J. Biol. Chem.. 274. 24270-24279 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Niki, T.: "MSSP promotes the ras/myc cooperative cell tansforming activity by binding to C-MYC"Genes Cells. 5. 127-140 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitaura, H.: "Reciprocal reguletion via protein-protein interaction between c-Myc and p21cip1/waf1/sdi1 in DNA replication and tanscription"J.Biol.Chem.. 275. in press (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kyo, S.: "Sp1 cooperates with c-Myc to activate transcription of human telomerase reverse transcriptase (hTERT) gene"Nucleic Acids Res.. 28. 339-345 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koike, N.: "Identification of heterochromatin protein 1(HP1) as a phosphorylation target by Pim-1 kinase and the effect of phosphorylation on the transcriptional"FEBS Lett.. 467. 17-21 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujimoto, M.: "Structure and comparison of genomic and complementary DNAs of mouse MSSP, a c-Myc binding protein"Int. J. Onc.. 16. 245-251 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mori,K: "MM-1,a novel C-MYC associating protein which represses transcriptional activity of C-MYC" J.Biol.Chem.273. 29794-29800 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ikuta,T.: "Structural analysis of mouse tenascin-X: Evolutionary aspects of reduplication of FNIII repeats in the tenascin gene family" Gene. 217. 1-13 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kimura,K.: "c-Myc gene single-strand binding protein-1,MSSP-1,suppresses transcription of a-smooth muscle actin gene in chicken visceral smooth muscle cells" Nucleic Acids Res.26. 2420-2425 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujimoto,M.: "Characterization of an element positively regulating the transcription of MSSP gene-2 which encodes C-MYC binding proteins." Gene. 214. 113-120 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Taira,T.: "AMY-1,a novel C-MYC binding protein that stimulates transcriptional activity of C-MYC" Genes Cells. 3. 551-567 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsuchiya,T.: "Ku antigen binds to Alu family DNA" J.Biochem.123. 120-127 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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