• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2002 Fiscal Year Final Research Report Summary

Molecular mechanism of transactivation via transcriptional coactivator complexes

Research Project

Project/Area Number 12480206
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

NAKAJIMA Toshihiro  St. Marianna University School of Medicine Department of Genome Science, Institute of Medical Science, Associate Professor, 難病治療研究センター, 助教授 (90260752)

Co-Investigator(Kenkyū-buntansha) FUKAMIZU Akiyoshi  Tsukuba University, Professor, 応用生物化学系, 教授 (60199172)
Project Period (FY) 2000 – 2002
Keywordstranscriptional activation / acetylation / CREB binding protein (CBP) / transcriptional coactivator / RNAhelicase A(RHA) / DNA methylation / epigenetics
Research Abstract

In the eukaryotic gene expression, recruitment of the basal transcriptional machinery including RNA polymerase (Pol) II is a principle mechanism for transcriptional activation. A specific transcriptional factor interacts with components of this machinery and localizes them to a specific promoter. For example, cAMP responsive element binding protein (CREB) stimulates target gene expression by recruitment of CREB binding protein (CBP). CBP interacting phosphorylated CREB activates the transcription via two mechanisms. One is dependent on the histone acetyltransferase activity (HAT), another is recruitment of Pol II mediated by RNA helicase A (RHA). RHA is a member of the DExH family of ATPases / helicases and catalyzes the displacement of both double-stranded RNA and DNA from 3' to 5'. We found that RHA recruits Pol II to breast cancer specific tumor suppressor protein (BRCA1) and enhance HIV virus gene expression.
For further an understanding of the role of RHA on gene expression, we have identified a 50 amino acid transactivation domain that interacts with Pol II and termed it the minimal transactivation domain (MTAD) in this project. The protein sequence of this region contains six hydrophobic residues and is unique to RHA homologues and well conserved. A mutant with this region deleted from full-length RHA decreased transcriptional activity in CREB-dependent transcription. In addition, mutational analyses revealed that several tryptophan residues in MTAD are important for the interaction with Pol II and transactivation. These results suggest that RHA could independently regulate CREB-dependent transcription either through recruitment of Pol II or ATP dependent mechanisms.

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H.Fujita: "Opposite effects of MBD2a on gene regulation"Molecular and Cellular Biology. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Aratani: "Dual roles of RNA helicase A on CREB-dependent transcription"Molecular and Cellular Biology. 21. 4460-4469 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Fujii: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"The Journal of Biological Chemistry. 276. 5445-5451 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Kitagawa: "Ligand Selective Potentiation of Rat Mineralocorticoid Receptor Activation Function-1 (AF-1) by ACBP-containing HAT complex"Mol. Cell. Biol.. 22. 3698-3706 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Kawabata: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium induced keratinocyte differentiation"The Journal of Biological Chemistry. 277. 8099-8105 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Araya: "Cooperative Interaction of EWS with CBP Selectively Activates HNF4-mediated Transcription"J Biol Chem.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Nakazawa: "Role of Notch-1 intracellular domain in activation of rheumatoid Synoviocytes"Arthritis & Rheum. 44. 1545-1554 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima T: "Effects of interaction between parvovirus minute virus of mice NS1 and coactivator CBP on NS1-and p53 -transactivation"International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] KP.Sarker: "Inhibition of Caspase-3 Activation by SB203580, p38 Mitogen-Activated ProteinKinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells"Journal of Molecular Neuroscience. 15. 243-250 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nguyen Dinh Khoa: "Potential role of HOXD9 in synoviocyte proliferation"Arthritis & Rheum. 44. 1013-1021 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Daitoku: "Dimerization of small GTPase Rab5"International Journal of Molecular Medicine. 8. 397-404 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ishii: "Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patients"Rheumatology International. 21. 10-14 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Fujita, R. Fujii, S. Aratani, T. Amano, A. Fukamizu, T. Nakajima: "Opposite effects of MBD2a on gene regulation"Molecular and Cellular Biology. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Aratani, R. Fujii, T. Oishi, H. Fujita, T. Amano, T. Ohshima, M. Hagiwara, A. Fukamizu, and T. Nakajima: "Dual roles of RNA helicase A in CREB-dependent transcription"Mol.Cell.Biol.. 21. 4460-4469 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R Fujii, M Okamoto, S Aratani, T Oishi, T Ohshima, K Taira, M Baba, A Fukamizu, T. Nakajima: "A role for RNA helicase A in TAR-dependent transcriptional regulation of the human immunodeficiency virus type 1"J Biol Chem.. 276. 5445-5451 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Kitagawa, J. Yanagisawa, H. Fuse, S. Ogawa, Y. Yogiashi, A. Okuno, H. Nagasawa, T. Nakajima. T. Matsumoto, S. Kato: "Ligand Selective Potentiation of Rat Mineralocorticoid Receptor Activation Function-1 (AF-1) by ACBP-containing HAT complex"Mol.Cell.Biol. 22. 3698-3706 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Kawabata, K. Kawahara, T. Kanekura, N. Araya, H. Daitoku, M. Hatta, N. Miura, A. Fukamizu, T. Kanzaki, I. Maruyama, T. Nakajima: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium induced keratinocyte differentiation"J Biol Chem.. 277. 8099-8105 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Araya, K. Hirota, Y. Shimamoto, M. Miyagisbi, E. Yoshida, J. Ishida, S. Kaneko, M. Kaneko, T. Nakajima, A. Fukamizu: "Cooperative Interaction of EWS with CBP Selectively Activates HNF4-mediated Transcription"J Biol Chem.. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Nakazawa, H. Ishii, H. Aono, M. Takai, T. Honda, S. Aratani, A. Fukamizu, H. Nakamura, S-I, Yoshino, T. Kobata, K. Nishioka, T. Nakajima: "Role of Notch-1 intracellular domain in activation of rheumatoid synoviocytes"Arthritis and Rheumatism. 44. 1545-1554 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohshima T, Yoshida Y, Nakajima T, Yagami K, Fukamizu A: "Effects of interaction between parvovirus minute virus of mice NS1 and coactivator CBP on NS1-and p53 -transactivation"International Journal of Molecular Medicine. 7. 49-54 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] KP. Sarker, M. Nakata, I. Kitajima, T. Nakajima, I. Maruyama: "Inhibition of Caspase-3 Activation by SB203580, p38 Mitogen-Activated Protein Kinase Inhibitor in Nitoric Oxide-Induced Apoptosis of PC-12 Cells"Journal of Molecular Neurosdence. 15. 243-250 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nguyen Dinh Khoa, Minako Nakazawa, Tomoko Hasunuma, Toshihiro Nakajima, Hiroshi Nakamura, Tetsuji Kobata, Kusuki Nishioka: "Potential role of HOXD9 in synoviocyte proliferation"Arthritis and Rheumatism. 44. 1013-1021 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Daitoku, J. Ishida, K. Fujiwara, T. Nakajima. A. Fukamizu: "Dimerization of small GTPase Rab5"International Journal of Molecular Medicine. 8. 397-404 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Ishii, M. Nakazawa, S. Yoshino, H. Nakamura, K. Nishioka, T. Nakajima: "Expression of Notch homologues in the synovium of rheumatoid arthritis and osteoarthritis patient"Rheumatology International. 21. 10-14 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2004-04-14  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi