Specific inhibition of transcriptional activity of the constitutive androstane receptor (CAR) by the splicing factor SF3a3.
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.
Yun
Hye Jin
HJ
Institute for Brain Science and Technology, Inje University, 633-146, Gaegumdong, Busanjingu, Busan 614-735, Republic of Korea.
Kwon
Jungsun
J
Seol
Wongi
W
D000818:Animals; D002460:Cell Line; D000090702:Constitutive Androstane Receptor; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D000090702:Constitutive Androstane Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D017413:Ribonucleoprotein, U2 Small Nuclear; D014157:Transcription Factors; C088049:splicing factor 3a