| 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 |
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| Section | 一般 |
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| Research Field |
Applied molecular and cellular biology
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| Research Institution | University of Tsukuba |
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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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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥46,930,000 (Direct Cost: ¥36,100,000、Indirect Cost: ¥10,830,000)
Fiscal Year 2004: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2003: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2002: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
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| Keywords | Foxol / CREB-binding protein (CBP) / acetylation / forkhead transcription factor / transcriptional cofactor / ubiquitination / insulin / multiple modification / FKHR |
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| 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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