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ATM-DEPENDENT PHOSPHORYLATION OF BRCA1 AND ITS BIOLOGICAL SIGNIFICANCE

Research Project

Project/Area Number 12680547
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionNAGASAKI UNIVERSITY

Principal Investigator

SUZUKI Keiji  NAGASAKI UNIVERSITY, SCHOOL OF PHARMACEUTICAL SCIENCES, RESEARCH ASSOCIATE, 薬学部, 助手 (00196809)

Co-Investigator(Kenkyū-buntansha) WATANABE Masami  NAGASAKI UNIVERSITY, SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 薬学部, 教授 (20111768)
KODAMA Seiji  NAGASAKI UNIVERSITY, SCHOOL OF PHARMACEUTICAL SCIENCES, ASSISTANT PROFESSOR, 薬学部, 助教授 (00195744)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsBRCA1 / ATM / IONIZING RADIATION / WORTMANNIN
Research Abstract

BRCA1 PROTEINS FORM DISCRETE FOCI IN THE NUCLEUS OF UNIRRADIATED NORMAL HUMAN DIPLOID CELLS. IN RESPONSE TO IONIXING RADIATION, BRCA1 PROTEINS RELOCATE AND FORM PUNCTATED FOCI, WHICH ARECLOSELY RELATED TO THOSE FORMED BY RAD50/MREll/NBS1 PROTEINS, BUT IN DIFFERENT LOCALIZATION. BECAUSE P53 ACCUMULATION AND PHOSPHORYLATION WAS SUPPRESSED IN HCC1937, WHICH DOES NOT CONTAIN BRCA1 PROTEIN, IT IS SUGGESTED THAT BRCA1 PROTEINS PLAY A ROLE IN ATM-DEPENDENT SIGNAL TRANSDUCT
BRCA1 WAS ALSO FOUND TO COLOCALIZE IN THE CENTROSOMES AFTER X-IRRADIATION. CENTROSOMES ARE THE ORGANELLA, WHICH DUPLICATE DURING CELL CECYLE PROGRESSION THROUGH G1 TO S PHASE. A PAIR OF CENTROSOME FUNCTIONS AS A DIVISION POLAR FROM WHICH SPINDLE FIBERS ARE FORMED. IN HCC1937 CELLS, CENTROSOMAL ABNORMALITY WAS FREQUENTLY DETECTED, SUGGESTING THAT BRCA1 PROTEINS ARE INVOLVED IN CENTROSOMAL STABILITY AFTER IRRADIATION. BECAUSE CENTROSOMAL ABNORMALITY RESULTS IN ANEUPLOIDY OF THE CHROMOSOMES, ATM-DEPEPDENT PHOSPHORYLATION OF BRCA1 PROTEIN MAY SUPPRESS OVER REPLICATION OF THE CENTOROSOMES.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Miyakoda M.: "Activation of ATM and phosphorylation of p53 by heat shock"Oncogene. 21. 1090-1096 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki K.: "Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells"Cancer Research. 61. 5396-5401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki, K.: "Radiation-induced senescence-like growth arrest requires Tp53 function but not telomere shortening"Radiation Research. 155. 248-253 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ghosh J. C.: "Dose-dependent biphasic accumulation of Tp53 protein in normal human embryo cells after X irradiation"Radiation Research. 153. 305-311 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] MIYAKODA, M.: "ACTIVATION OF ATM AND PHOSPHORYLATION OF ATM BY HEAT SHOCK"ONOOGENE. 21. 1090-1096 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] SUZUKI, K.: "EXTREMELY LOW-DOSE IONIZING RADIATION CAUSES ACTIVATION OF MITOGEN-ACTIVATED PROTEIN KINASE PATHWAYS AND ENHANCES PROLIFERATION OF NORMAL HUMAN DIPLOID CELLS"CANCER RESEARCH. 21. 1090-1096 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] SUZUKI, K.: "RADIATION-INDUCED SENESCENCE-LIKE GROWTH ARREST REQUIRES TP53 FUNCTION BUT NOT TELOMERE SHORTENING"RADIATION RESEARCH. 155. 248-253 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] GHOSH, J.: "DOSE-DEPENDENT BIPHASIC ACCUMULATION OF TP53 PROTEIN IN NORMAL HUMAN EMBRYO CLASS AFTER X-IRRADIATION"RADIATION RESEARCHE. 153. 305-311 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakoda M.: "Activation of ATM and phosphorylation of p53 yb heat shock"Oncogene. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki K.: "Extremely low-dose ionizing radiation causes activation of mitogen-activated protein kinase pathway and enhances proliferation of normal human diploid cells."Cancer Research. 61. 5396-5401 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki, K.: "Radiation-induced senescence-like growth arrest requires Tp53 function but not telomere shortening"Radiation Research. 155. 248-253 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ghosh J.C.: "Dose-dependent biphasic accumulation of Tp53 protein in normal human embryo cells after X irradiation"Radiation Research. 153. 305-311 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki,K.: "Radiation-induced senescence-like growth arrest requires Tp53 function but not telomere shortening"Radiation Research. 155. 248-253 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ghosh J.C.: "Dose-dependent biphasic accumulation of Tp53 protein in normal human embryo cells after X irradiation"Radiation Research. 153. 305-311 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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