| Project/Area Number |
15590092
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | National Institute of infectious Diseases |
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Principal Investigator |
MASUMI Atsuko National Institute of Infectious Diseases, Department of Safety Research on Bood and Biological Products, Senior Scientist, 血液・安全性研究部, 主任研究官 (70165728)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | IRF / Acetylation / Chromatin / cell growth / Interferon / アセチル化 / IRF / クロマチン / 細胞増殖分化 / インターフェロン |
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| Research Abstract |
We have previously shown that Interferon regulatory factor-2(IRF-2) is acetylated in a cell growth-dependent manner, which enables it to contribute to the transcription of cell growth-regulated promoters. To clarify the function of the acetylation of IRF-2, we investigated the proteins that associate with acetylated IRF-2. Transfection of p300/CBP-associated factor(PCAF) enhanced acetylation of IRF-2 in 293T cells. In cells transfected with both IRF-2 and PCAF, IRF-2 associated with endogenous nucleolin, in contrast, little association was observed when IRF-2 was transfected with a PCAF HAT deletion mutant. In a pull-down experiment using stable transfectants, acetylation defective mutant IRF-2(IRF-2K75R) recruited nucleolin to much lower degree than that of wild type IRF-2, suggesting that nucleolin preferentially associates with acetylated IRF-2. Confocal analysis indicated that IRF-2 colocalized with nucleolin in the perinucleolar region. Nucleolin in the presence of PCAF enhanced IRF-2-dependent H4 promoter activity in NIH3T3 cells. Affinity DNA binding analysis with H4 promoter DNA indicated that nucleolin associated with IRF-2 in growing NIH3T3 cells, but not in growth-arrested counterparts. We conclude that nucleolin is recruited to acetylated IRF-2, contributing to gene regulation crucial for the control of cell growth.
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