Proceedings of Annual Meeting of the Physiological Society of Japan
Proceedings of Annual Meeting of the Physiological Society of Japan
Session ID : 2P-F-079
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A novel mechanism of nuclear hormone receptor-mediated transcriptional regulation by TRBP-CoAA/CoAM-SRA cofactors.
*Toshiharu IwasakiMarina LondonoWataru MiyazakiNoriaki ShimokawaNoriyuki Koibuchi
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Abstract
Recently, we have cloned and characterized a coactivator activator (CoAA) using a Sos-Ras Yeast Two-hybrid Screening System and TR-binding protein (TRBP)-C-terminus as bait. Interestingly, a shorter splicing variant is also produced from CoAA gene, named coactivator modulator (CoAM), which functions as a transcriptional suppressor. A series of protein-RNA binding studies revealed that CoAA or CoAM binds to RNA. However, these bindings are not specific. Since transcriptional regulations are mainly activated by histone acetyl transferase (HAT) complex, we examined the effect of CoAA/CoAM on the HAT activity. CoAA activated the HAT activity in the presence of CREB-binding protein (CBP), however, CoAM did not. Thus, we presumed the suppression by CoAM may be related to other than nuclear event. To investigate the location of CoAA or CoAM, immunofluorescent studies were performed. Interestingly, CoAA was located in the nucleus, whereas CoAM is in the cytoplasm. These results suggest that the location of CoAA/CoAM may determine the transcriptional activity, possibly by interacting with cofactor(s) essential for chromatin remodeling. In summary, CoAA/CoAM determines the transcriptional activity by a novel mechanism. [J Physiol Sci. 2008;58 Suppl:S138]
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© 2008 The Physiological Society of Japan
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