Similarities in physiological roles of LXR (liver X receptors) and co-repressor RIP140 (receptor-interacting protein 140) in regulating energy homoeostasis and lipid and glucose metabolism suggest that the effects of LXR could at least partly be mediated by recruitment of the co-repressor RIP140. In the present study, we have elucidated the molecular basis for regulation of LXR transcriptional activity by RIP140. LXR is evenly localized in the nucleus and neither the N-terminal domain nor the LBD (ligand-binding domain) is necessary for nuclear localization. Both LXR subtypes, LXRα and LXRβ, interact with RIP140 and co-localize in diffuse large nuclear domains. Interaction and co-localization are dependent on the LBD of the receptor. The C-terminal domain of RIP140 is sufficient for full repressive effect. None of the C-terminal NR (nuclear receptor)-boxes is required for the co-repressor activity, whereas the NR-box-like motif as well as additional elements in the C-terminal region are required for full repressive function. The C-terminal NR-box-like motif is necessary for interaction with LXRβ, whereas additional elements are needed for strong interaction with LXRα. In conclusion, our results suggest that co-repression of LXR activity by RIP140 involves an atypical binding mode of RIP140 and a repression element in the RIP140 C-terminus.
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Research Article|
June 13 2007
Molecular basis for repression of liver X receptor-mediated gene transcription by receptor-interacting protein 140
Tomas Jakobsson;
Tomas Jakobsson
1
1Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Sweden
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Waffa Osman;
Waffa Osman
1
1Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Sweden
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Jan-Åke Gustafsson;
Jan-Åke Gustafsson
1Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Sweden
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Johanna Zilliacus;
Johanna Zilliacus
1Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Sweden
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Anette Wärnmark
Anette Wärnmark
2
1Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 57 Huddinge, Sweden
2To whom correspondence should be addressed (email anette.warnmark@biosci.ki.se).
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Publisher: Portland Press Ltd
Received:
January 02 2007
Revision Received:
March 27 2007
Accepted:
March 28 2007
Accepted Manuscript online:
March 28 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2007 Biochemical Society
2007
Biochem J (2007) 405 (1): 31–39.
Article history
Received:
January 02 2007
Revision Received:
March 27 2007
Accepted:
March 28 2007
Accepted Manuscript online:
March 28 2007
Citation
Tomas Jakobsson, Waffa Osman, Jan-Åke Gustafsson, Johanna Zilliacus, Anette Wärnmark; Molecular basis for repression of liver X receptor-mediated gene transcription by receptor-interacting protein 140. Biochem J 1 July 2007; 405 (1): 31–39. doi: https://doi.org/10.1042/BJ20070004
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