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

Tomas Jakobsson , Waffa Osman , Jan-Åke Gustafsson , Johanna Zilliacus , Anette Wärnmark (1)

1 Department of Biosciences and Nutrition

Similarities in physiological roles of Liver X receptors (LXR) and corepressor Receptor-interacting protein 140 (RIP140) in regulating energy homeostasis and lipid and glucose metabolism suggest that the effects of LXR could at least partly be mediated by recruitment of the corepressor 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 ligand-binding domain is necessary for nuclear localization. Both LXR subtypes, LXRα and β, interact with RIP140 and colocalize in diffuse large nuclear domains. Interaction and colocalization are dependent on the ligand-binding domain of the receptor. The C-terminal domain of RIP140 is sufficient for full repressive effect. None of the C-terminal NR-boxes is required for the corepressor 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 corepression of LXR activity by RIP140 involves an atypical binding mode of RIP140 and a repression element in the RIP140 C-terminus.

Mots clés: Life Sciences

Tomas Jakobsson, Waffa Osman, Jan-Åke Gustafsson, Johanna Zilliacus, Anette Wärnmark. Molecular basis for repression of liver X receptor-mediated gene transcription by the receptor-interacting protein 140. Biochemical Journal, 2007, 405 (1), pp.31-39. ⟨10.1042/BJ20070004⟩. ⟨hal-00478730⟩