发明名称 |
ALLOSTERIC CONTROL OF NUCLEAR HORMONE RECEPTORS |
摘要 |
Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurr1 heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response. These findings establish a novel 9-cis retinoic acid response pathway and resolve the paradox as to how T3R, RAR and VDR contribute to distinct physiologic pathways while sharing a common RXR subunit.
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申请公布号 |
WO9621457(A1) |
申请公布日期 |
1996.07.18 |
申请号 |
WO1995US17024 |
申请日期 |
1995.12.28 |
申请人 |
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES |
发明人 |
EVANS, RONALD, M.;FORMAN, BARRY, M.;UMESONO, KAZUHIKO |
分类号 |
C07K14/705;G01N33/68;G01N33/74;(IPC1-7):A61K38/17;C12N15/79 |
主分类号 |
C07K14/705 |
代理机构 |
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