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/lp/de-gruyter/specific-inhibition-of-transcriptional-activity-of-the-constitutive-Llgh8VapqD
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- Publisher
- de Gruyter
- Copyright
- ©2008 by Walter de Gruyter Berlin New York
- Subject
- Genes and Nucleic Acids
- ISSN
- 1431-6730
- eISSN
- 1437-4315
- DOI
- 10.1515/BC.2008.149
- pmid
- 18713018
- Publisher site
- See Article on Publisher Site
Abstract
The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily and plays an important role in the degradation of xenobiotics in the liver. Using yeast two-hybrid screening, we identified SF3a3, a 60-kDa subunit of the splicing factor 3a complex, as a specific CAR-interacting protein. We further confirmed their interaction by both co-immunoprecipitation and GST pull-down assay. Functional studies showed that overexpression of SF3a3 inhibited the reporter activity driven by a promoter containing CAR binding sequences by up to 50%, whereas reduced expression of SF3a3 activated the same reporter activity by approximately three-fold. The inhibitory function of SF3a3 is independent of the presence of TCPOBOP, a CAR ligand. These data suggest that SF3a3 functions as a co-repressor of CAR transcriptional activity, in addition to its canonical function.
Journal
Biological Chemistry – de Gruyter
Published: Oct 1, 2008
Keywords: co-repressor; nuclear receptor; transcriptional regulation