| Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Masatoshi Medical Research Institute, Tokyo Medical and Dental University, Professor, 難治疾患研究所, 教授 (10208423)
KATO Shigeaki Institute of Molecular and Cellular Biosciences, The University of Tokyo, Professor, 分子細胞生物学研究所, 教授 (60204468)
AKIRA Sizuo Research Institute for Microbial Diseases, Osaka University, Professor, 微生物研究所, 教授 (50192919)
HISATAKE Koji Deprtment of Biochemistry, Saitama Medical School, Assistant professor, 第2生化学, 助教授 (70271236)
HANDA Hirosi Frontier Collaborative Research Center, Tokyo Institute of Technology, Professor, フロンティア創造共同研究センター, 教授 (80107432)
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| Research Abstract |
The purpose of this research group is to elucidate the molecular mechanism of interaction between transcription factors including transcription coordinators finally leading to the expression of specific genes. TFIIH composed of 9 subemits was successfully reconstituted from the recombinantly expressed subunit proteins in a baculovirus system. This system provides good an excellent tool for investigating the function of these individual subunits in the transcription complex and revealed that the helicase activity of ERCC3 plays and essential role of promotor escape in the transcription initiation. Subsequent to the transcription initiation, the transcription reaction was elucidated to be precisely regulated in positive and negative fashions by sing DSIF and NELF as negative factors, and pTEFb and FACT as positive factors. Mutation in the C-terminal region a subunit, p160 of DSIF was found to cause abberant neural development of zebrafish. It has been further clarified that CBP which functions as a coactivator to a variety of transcription factors also plays a coactivator or to the transcription factors, GLI3, AhR/Arnt, HIF-12 and IFR3. A complex CBP with β-catenine was found to localize at the PML region and β-catenine in hybrid the transcription activity of p53 by isolating CBP. By the two-hybrid methods, additional coactivators, MBF1, UTF1 and p68/p72 have been isolated for the transcription factors, FTZ-F1, RAR and ER α,β and their primary structures and functions have been investigated extensively. Functional analyses of transcription factors such as STAT3, AhR, VDR and many other have been extensively investigated by the gene-targeting technology.
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