2004 Fiscal Year Final Research Report Summary
Functional Network of Transcriptional Control Factors Regulated by Multiple Modifications
Project/Area Number |
14206040
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied molecular and cellular biology
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Research Institution | University of Tsukuba |
Principal Investigator |
FUKAMIZU Akiyoshi University of Tsukuba, Graduate School of Life and Enviromental Sciences, Professor, 大学院・生命環境科学研究科, 教授 (60199172)
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Co-Investigator(Kenkyū-buntansha) |
TANIMOTO Keiji University of Tsukuba, Graduate School of Life and Enviromental Sciences, Associate Professor, 大学院・生命環境科学研究科, 助教授 (90261776)
ISHIDA Junji University of Tsukuba, Graduate School of Life and Enviromental Sciences, Assistant Professor, 大学院・生命環境科学研究科, 講師 (30323257)
SUGIYAMA Fumihiro University of Tsukuba, Graduate School of Comprehensive Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (90226481)
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Project Period (FY) |
2002 – 2004
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Keywords | Foxol / CREB-binding protein (CBP) / acetylation / forkhead transcription factor / transcriptional cofactor / ubiquitination / insulin / multiple modification |
Research Abstract |
Exposure of cells to external signaling causes changes in gene expression for appropriate physiological responses. Once activated on the plasma membrane of cells, the siganals initiate a cascade of signals that are transmitted to the nucleus where they switch on and off the expression of target genes by modifying the activity of transcription factors. Targeted modifications of transcription factors, including acetylation, phosphorylation, methylation, and ubiquitination, for rapid alterations in their activities in response to external and internal stimuli have emerged as an important mechanism in the regulation of transcriptional activation of RNA polymerase II-transcribed genes. In response to insulin, protein kinase B-mediated phosphorylation is shown to modulate the function of the FOXO forkhead transcription family members. The unphosphorylated FOXO factors that localize to the nucleus bind to the insulin response sequence (IRS) within the promoters of the target genes, which control the cell cycle, cell death, oxidative stress, and glucose metabolism. On the other hand, they are phosphorylated by insulin, resulting in promoting their cytoplasmic retention. Although the relevance of FOXO family regulated by multiple modifications to the physiological functions in the transcription-based nuclear action is of significant interest, the fate of FOXO factors in the cells is not yet fully understood. In the present study, we demonstrated the regulatory roles for the FOXO factors by multiple modifications.
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[Journal Article] SREBPs suppress IRS-2-mediated insulin signaling in the liver2004
Author(s)
Ide, T., Shimano, H., Yahagi, N.Matsuzaka, T., Nakakuki, M., Yamamoto, T., Nakagawa, Y., Takahashi, A., Suzuki, H., Sone, H., Toyoshima, H., Fukamizu, A., Yamada, N.
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Journal Title
Nat.Cell Biol. 6
Pages: 351-357
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression.2004
Author(s)
Ieda, M., Fukuda, K., Hisaka, Y., Kimura, K., Kawaguchi, H., Fujita, J., Shimoda, K., Takeshita, E., Okano, H., Kurihara, Y., Kurihara, H., Ishida, J., Fukamizu, A., Federoff, H.J., Ogawa, S.
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Journal Title
J.Clin.Invest. 113
Pages: 876-884
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxol.2004
Author(s)
Yamagata, K., Daitoku, H., Shimamoto, Y., Matsuzaki, H., Hirota, K., Ishida, J., Fukamizu, A.
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Journal Title
J.Biol.Chem. 279
Pages: 23158-23165
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II.2004
Author(s)
Zou, Y., Akazawa, H., Qin, Y., Sano, M., Takano, H., Minamino, T., Makita, N., Iwanaga, K., Zhu, W., Kudoh, S., Toko, H., Tamura, K., Kihara, M., Nagai, T., Fukamizu, A., Umemura, S., Iiri, T., Fujita, T., Komuro, I.
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Journal Title
Nat.Cell Biol. 6
Pages: 499-506
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reglatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type in blood pressure in vivo.2004
Author(s)
Ishida, J., Hashimoto, T., Hashimoto, Y., Nishiwaki, S., Iguchi, T., Harada, S., Sugaya, T., Matsuzaki, H., Yamamoto, R., Shiota, N., Okunishi, H., Kihara, M., Umemura, S., Sugiyama, F., Yagami, K., Kasuya, Y., Mochizuki, N., Fukamizu, A.
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Journal Title
J.Biol.Chem. 279
Pages: 26274-26279
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Silent information regular 2 potentiates Foxol-mediated transcription through its deacetylase activity.2004
Author(s)
Daitoku, H., Hatta, M., Matsuzaki, H., Aratani, S., Ohshima, T., Miyazaki, M., Nakajima, T., Fukamizu, A.
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Journal Title
Proc.Natl.Acad.Sci. 101
Pages: 10042-10047
Description
「研究成果報告書概要(欧文)」より