| Project/Area Number |
13357010
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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 | 展開研究 |
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| Research Field |
Endocrinology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
NAWATA Hajime Kyushu University, Department of medicine, professor, 大学院・医学研究院, 教授 (10038820)
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| Co-Investigator(Kenkyū-buntansha) |
YANASE Toshihiko Kyushu University, associate professor, 大学院・医学研究院, 助教授 (30239818)
GOTO Kiminobu Kyushu University, assistant professor, 大学病院, 助手 (90284512)
OKABE Taijiroh Kyushu University, assistant professor, 大学病院, 助手 (40264030)
NOMURA Masahiro Kyushu University, assistant professor, 大学病院, 助手 (30315080)
戸村 有宏 日本化薬株式会社, 医薬事業本部・創薬本部・新薬創生部門, 副主任研究員
高柳 涼一 九州大学, 大学院・医学研究院, 教授 (30154917)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥46,280,000 (Direct Cost: ¥35,600,000、Indirect Cost: ¥10,680,000)
Fiscal Year 2003: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2002: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2001: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000)
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| Keywords | androgen receptor / ANT-1 / splicing factor compartment / TPR structure / functional domein / Yeast Two-hybrid assay / AR AF-1 / GSTプルダウン / cDNA cloning / Yeast two-hybrid assay / ARAF-1 / TPR |
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| Research Abstract |
In the androgen receptor (AR), most of its transactivation activity is mediated via the activation function -1(AF-1). By employing yeast two-hybrid assay, we isolated a cDNA sequence encoding a protein binding to AR-AF-1. This protein, named ANT-1(AR N-terminal domain transactivating protein-1), enhanced the ligand-independent autonomous AF-1 transactivation function of AR or glucocorticoid receptor, but did not enhance that of estrogen receptor α. In contrast, the ANT-1 did not enhance any ligand-dependent AF-2 activities. Furthermore, the ligand-independent interaction between AR-AF-1 and ANT-1 was confirmed in vivo and in vitro. The ANT-1 sequence was identical to that of a protein that binds to U5 small nuclear ribonucleoprotein particle, a human homologue of yeast splicing factor Prp6p, involved in spliceosome. ANT-1 was compartmentalized into 20-40 coarse splicing factor compartment speckles against the background of the diffuse reticular distribution. AR colocalized with ANT-1 only in the diffusely distributed area, whereas the ANT-1 speckles were spatially distinct from but surrounded by the AR compartments. The active gene transcription has been shown to periphery of the splicing factor compartment. The molecular interaction between two spatially distinct subnuclear compartments mediated by ANT-1 may therefore recruit AR into the transcription-splicing-coupling machinery.
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