1993 Fiscal Year Annual Research Report

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 Institution	Kyoto 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)
Keywords	DNA複製 / p53 / 転写制御因子 / 急性骨髄性白血病 / t(8;21)転座
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。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Bae,S.C.: "PEBP2αB/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials." Mol.Cell.Biol.(in press). (1994)
[Publications] Kanda,T.: "Stimulation of polyomavirus DNA replication by wild-type p53 through the DNA-binding site." Mol.Cell.Biol.(in press). (1994)
[Publications] Inuzuka,M.: "The viral and cellular Rel oncoproteins induce the differentiation of P19 embryonal carcinoma cells." Oncogene. 9. 133-140 (1994)
[Publications] Kagoshima,H.: "The Runt-domain identifies a new family of heteromeric DNA-binding transcriptional regulatory proteins." Trends in Genetics. 8. 338-341 (1993)
[Publications] Ishikawa,H.: "Two novel functions associated with the Rel oncoproteins:DNA replication and cell-specific transcriptional activation." Oncogene. 8. 2889-2896 (1993)
[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)
[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)
[Publications] Morgan,I.M.: "Amino acid substitutions modulate the effect of Jun on transformation,transcriptional activation and DNA replication." Oncogene. 8. 1135-1140 (1993)
[Publications] Ibaraki,T.: "Transacting activities of the E7 genes of several types of human papillomavirus." VIRUS GENES. 7. 187-196 (1993)
[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)
[Publications] Bae,C.C.: "Isolation of PEBP2αB cDNA representing the mouse homolog of human acute myeloid leukemia gene,AML1." Oncogene. 8. 809-814 (1993)

1993 Fiscal Year Annual Research Report

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

Principal Investigator

伊藤 嘉明 京都大学, ウイルス研究所, 教授 (80004612)

Research Products

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

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

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

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

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

[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)

[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)

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

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

[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)

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

伊藤嘉明京都大学, ウイルス研究所, 教授 (80004612)