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転写・複製制御因子の解析を中心にしたHPVによる発がん機構の研究

Research Project

Project/Area Number 04253215
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKyoto University

Principal Investigator

伊藤 嘉明  京都大学, ウイルス研究所, 教授 (80004612)

Co-Investigator(Kenkyū-buntansha) 丸山 光生  京都大学, ウイルス研究所, 助手 (00212225)
浅野 摩樹  京都大学, ウイルス研, 日本学術振興会特別研
重定 勝哉  京都大学, ウイルス研, 助教授 (40009626)
Project Period (FY) 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥30,000,000 (Direct Cost: ¥30,000,000)
Fiscal Year 1993: ¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 1992: ¥15,000,000 (Direct Cost: ¥15,000,000)
KeywordsDNA複製 / p53 / 転写制御因子 / 急性骨髄性白血病 / t(8;21)転座 / in vitro DNA複製 / c-Jun / c-Fos / Rel / NFκB / runt / AML1
Research Abstract

p53のポリオーマウイルスDNA複製への影響を調べ転写活性化能を持つドメインと複製活性化能を持つそれが一部しか重複せず、2つが乖離する事を見出した。(Kandor et al Mol.Cell.Biol.1994,in press).p53のN端とC端に複製に必要な蛋白RP-Aが結合する事がDuttaらにより最近報告されたが(Nature965:79-82,1993),今回我々が見出した複製活性化ドメインとRP-A結合部位はよく一致する。興味深い事はHowbyらがp53のN端の転写活性化ドメインを欠損させてもp53によるトランスフォーメーションの抑制活性は完全には消失しないと報告している点である。今回我々が同定したC端にある複製活性化能とトランスフォーメーションの抑制活性に関係があるかどうか調べる必要がある。
我々の同定した新しい転写因子PEBP2のαサブユニットをコードするαB遺伝子は急性骨髄性白血病で8番21番相互転座の起る型で転座点の集中する遺伝子AML19マウスホモログである。t(8;21)の結果キメラ蛋白が合成される。そのキメラ蛋白の白血病原性を調べるためキメラRNAの接続点に相補的なアッチセンスオリゴヌクレオチドを合成し、培地に混入したところ,t(8;21)を持つ白血病細胞株の増殖が著しく抑制され細胞は分化しはじめた。従ってキメラ蛋白に白血病原性のある事が強く示唆された。

Report

(2 results)
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Bae,S.C.: "PEBP2αB/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials." Mol.Cell.Biol.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kanda,T.: "Stimulation of polyomavirus DNA replication by wild-type p53 through the DNA-binding site." Mol.Cell.Biol.(in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Inuzuka,M.: "The viral and cellular Rel oncoproteins induce the differentiation of P19 embryonal carcinoma cells." Oncogene. 9. 133-140 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kagoshima,H.: "The Runt-domain identifies a new family of heteromeric DNA-binding transcriptional regulatory proteins." Trends in Genetics. 8. 338-341 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ishikawa,H.: "Two novel functions associated with the Rel oncoproteins:DNA replication and cell-specific transcriptional activation." Oncogene. 8. 2889-2896 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Xul,X.: "Functional interaction of the v- and c-Rel oncoproteins with general transcription factors TBP and TFIIB." Mol.Cell.Biol.13. 6733-6741 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogawa,E.: "PEBP2/PEA2 represents a family of transcription factors-homologous to the products of the Drosophila runt gene and the human AML1 gene." Proc.Natl.Acad.Sci.USA. 90. 6859-6863 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morgan,I.M.: "Amino acid substitutions modulate the effect of Jun on transformation,transcriptional activation and DNA replication." Oncogene. 8. 1135-1140 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ibaraki,T.: "Transacting activities of the E7 genes of several types of human papillomavirus." VIRUS GENES. 7. 187-196 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ogawa,E.: "Molecular cloning and characterization of PEBP2β,the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2α." Virology. 194. 314-331 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Bae,C.C.: "Isolation of PEBP2αB cDNA representing the mouse homolog of human acute myeloid leukemia gene,AML1." Oncogene. 8. 809-814 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Satake,M.: "Differential expression of subspecies of polyomavirus and murine leukemia virus enhancer core binding protein,PEBP2,in various hematopoietic cells." Jpn.J.Cancer Res.83. 714-722 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Naito,M.: "Detection of p53 gene mutations in human ovarian and endometrial cancers by polymerase chain reaction-single strand conformation polymorphism analysis." Jpn.J.Canser Res.83. 1030-1036 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Bae,S.C.: "Isolation of PEBP2αB cDNA representing the mouse homolog of human acute myeloid leukemia gene,AML1." Oncogene. 8. 809-814 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ogawa,E.: "Molecular cloning and characterization of PEBP2β,the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2α." Virology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Ogawa,E.: "PEBP2/PEA2 represents a new family of transcription factor homologous to the products of the Drosophila runt and the human AML1." Proc.Natl.Acad.Sci.USA.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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