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Role of myb gene family in the proliferation control of hematopoietic cells

Research Project

Project/Area Number 07670388
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe Institte of Physical & Chemical Research (RIKEN)

Principal Investigator

NOMURA Teruaki  RIKEN,Molecular Genetics Lab. Senior research scientist, 分子遺伝学研究室, 先任研究員 (80231512)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsMyb / Transcriptional control / Co-activator / Signal trnasduction / Cellular proliferation / myb / 転写因子 / 造血系
Research Abstract

The reults obtained so far all indicate a role for c-myb in maintaining the proliferative state of hematopoietic prgenitor cells. Disruption of this leucine zipper by site-directed mutagenesis markedly increases both trans-activating and transforming capacities. Since the leucine zipper motif was originallyn identified as mediating dimerization of several DNA-binding proteins, these results indicate that c-Myb activity is negatively regulated through the leucine zipper and imply the presence of an inhibitor (s) of c-Myb.
Homozygous c-myb mutant mice generated by homologous recombination in embryonic stem cells die at the embryonic stage due to a specific failure of fetal hepatic haematopoiesis. Therefore, this mutant cannot used for the analyzes of c-myb function in the adult tissues. We have tried to make the point mutant mice of c-myb by two step homologous recombination in ES cells. In these point mutants, the c-Myb activity is expected to be 1/10 or 10-fold compared with the wild type, and the mutant mice is not lethal at embryonic stage. We have made the heterozygous point mutants, so that the expected homozgous mutants will be very useful for the analyzes of myb function.
We have found that c-Myb binds to CBP in a phosphorylation-independent manner. Since CBP interacts with TFIIB,CBP mediates CREB-or c-Myb-dependent transcriptional activation as a bridge between phosphorylated CREB or c-Myb and the RNA polymerase II complex. Recently, CBP was demonstated to function as a transcriptional coactivator for many other transcriptional activators including c-Jun and c-Fos. Interestingly, mutations in the human CBP gene cause Rubinstein-Taybi syndrome through haploinsufficiency, suggesting that theamount of CBP in cells is not excessive and a 50% decrease in the amount affects normal development. Therefore, cross talk between the c-Myb, c-Myb, cAMP,and AP-1 pathways through competition for binding to CBP is possible.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report

Research Products

(7 results)

All Other

All Publications

  • [Publications] Ramsay,R.G.: "Regulation of c-Myb through protein phosphorylation and leucine zipper interactions" Oncogene. 11. 2113-2120 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kanei-Ishii,C.: "Structure and function of the proteins encoded by the myb gene family" Current Topics in Microbilogy and Immunology. 211. 89-98 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ramsay, R.G., Morrice, N., Vaneeden, P., Kanagasundaram, V., Nomura, T.: "Deblaquire, J., Ishii, S.& Wettenhall, R."Regulation of c-Myb through protein phosphorylation and leucine zipper interactions"" Oncogene. 11. 2113-2120 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kanei-Ishii, C., Nomura, T., Ogata, K., Sarai, A., Yasukawa, T., Tashiro, S., Takahashi, T., Tanaka, Y.& Ishii, S.: ""Structure and function of the proteins encoded by the mybgene family"" Current Topics in Microbilogy & Immunology. 211. 89-98 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kanei-Ishii,C.et al.: "Structure and function of the proteins encoded by the myb gene family" Curr.Top.Micro.Imm.211. 89-98 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ramsay, R. G.: "Regulation of c-Myb through protein phosphorylation and leucine zipper interactions" Oncogene. 11. 2113-2120 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kanei-Ishii, C.: "Structure and function of the proteins encoded by the myb gene family" Current Topics in Microbilogy and Immunology. 211. 89-98 (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-03-31   Modified: 2016-04-21  

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