Molecular basis for repression of liver X receptor-mediated gene transcription by receptor-interacting protein 140

Tomas Jakobsson, Waffa Osman, Jan Åke Gustafsson, Johanna Zilliacus, Anette Wärnmark

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalBiochemical Journal
Volume405
Issue number1
DOIs
StatePublished - Jul 1 2007

Keywords

  • Co-regulatory protein
  • Ligand-binding domain (LBD)
  • Liver X receptor (LXR)
  • Nuclear receptor
  • Receptor-interacting protein 140 (RIP140)

ASJC Scopus subject areas

  • Biochemistry

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