Corepressor interaction differentiates the permissive and non-permissive retinoid X receptor heterodimers

Archives of Biochemistry and Biophysics
Johanna LammiPiia Aarnisalo

Abstract

Nurr1 is an orphan nuclear receptor regulating transcription both as a monomer and as a heterodimer with retinoid X receptor (RXR). RXR-Nurr1 heterodimers are permissive RXR heterodimers as they activate transcription in response to RXR ligands. In contrast, heterodimers formed by RXR and retinoic acid receptor (RAR) are non-permissive as they activate transcription only upon RAR ligand binding. We studied the mechanism mediating permissiveness and non-permissiveness by creating receptor chimeras between Nurr1 and RAR. We show that the amino-terminal part of the Nurr1 ligand binding domain conveys permissiveness to RXR-Nurr1 heterodimers. This region is involved in interactions with the corepressors SMRT and NcoR. The corepressors were released from RXR-Nurr1 heterodimers by RXR ligand binding. In contrast, RXR ligand increased the interaction between RXR-RAR heterodimers and the corepressors. The corepressors were released only upon binding of RAR ligand. In conclusion, corepressor interaction differentiates the permissive RXR-Nurr1 heterodimers from the non-permissive RXR-RAR heterodimers.

Citations

Jun 29, 2011·Pflügers Archiv : European journal of physiology·Urs Albrecht
Apr 28, 2011·Neurobiology of Learning and Memory·Susan C McQuown, Marcelo A Wood
Oct 25, 2011·Biochimica Et Biophysica Acta·Marcia I Dawson, Zebin Xia
Sep 13, 2018·Annual Review of Pharmacology and Toxicology·Miguel MoutinhoGary E Landreth
Apr 4, 2019·Medicinal Research Reviews·Nathalia Rodrigues de Almeida, Martin Conda-Sheridan
Jul 22, 2018·Archives of Toxicology·Stephanie KimJennifer J Schlezinger
Nov 27, 2020·Haematologica·Orsola Di MartinoJohn S Welch
Jul 13, 2021·Journal of Medicinal Chemistry·Sabine WillemsDaniel Merk
May 2, 2015·Chemical Research in Toxicology·Amelia H BakerJennifer J Schlezinger
Nov 7, 2018·Environmental Science & Technology·Ana M F CapitãoL Filipe C Castro

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