2002 Fiscal Year Final Research Report Summary
Molecular mechanism of transactivation via transcriptional coactivator complexes
| Project/Area Number |
12480206
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | St. Marianna University School of Medicine |
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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)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAMIZU Akiyoshi Tsukuba University, Professor, 応用生物化学系, 教授 (60199172)
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| Project Period (FY) |
2000 – 2002
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| Keywords | transcriptional activation / acetylation / CREB binding protein (CBP) / transcriptional coactivator / RNAhelicase A(RHA) / DNA methylation / epigenetics |
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| 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.
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Research Products
(24 results)
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[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)
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[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)
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