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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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1437-4315
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Volume 389, Issue 10

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Specific inhibition of transcriptional activity of the constitutive androstane receptor (CAR) by the splicing factor SF3a3

Hye Jin Yun
  • 1Institute for Brain Science and Technology, Inje University, 633-146, Gaegumdong, Busanjingu, Busan 614-735, Republic of Korea
  • Other articles by this author:
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/ Jungsun Kwon
  • Present address: Koram Biotech, 907-1, Daechidong, Gang-namgu, Seoul 135–280, Republic of Korea.
    2Institute for Brain Science and Technology, Inje University, 633-146, Gaegumdong, Busanjingu, Busan 614-735, Republic of Korea
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Wongi Seol
  • 3Institute for Brain Science and Technology, Inje University, 633-146, Gaegumdong, Busanjingu, Busan 614-735, Republic of Korea and Graduate Program in Neuroscience, Inje University, 633-146, Gaegumdong, Busanjingu, Busan 614-735, Republic of Korea
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2008-08-19 | DOI: https://doi.org/10.1515/BC.2008.149

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.

Keywords: co-repressor; nuclear receptor; transcriptional regulation

About the article

Corresponding author


Received: 2008-01-16

Accepted: 2008-05-29

Published Online: 2008-08-19

Published in Print: 2008-10-01


Citation Information: Biological Chemistry, Volume 389, Issue 10, Pages 1313–1318, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2008.149.

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