Unknown

Dataset Information

0

Agonist ligands mediate the transcriptional response of nuclear receptor heterodimers through distinct stoichiometric assemblies with coactivators.


ABSTRACT: The constitutive androstane (CAR) and retinoid X receptors (RXR) are ligand-mediated transcription factors of the nuclear receptor protein superfamily. Functional CAR:RXR heterodimers recruit coactivator proteins, such as the steroid receptor coactivator-1 (SRC1). Here, we show that agonist ligands can potentiate transactivation through both coactivator binding sites on CAR:RXR, which distinctly bind two SRC1 molecules. We also observe that SRC1 transitions from a structurally plastic to a compact form upon binding CAR:RXR. Using small angle x-ray scattering (SAXS) we show that the CAR(tcp):RXR(9c)·SRC1 complex can encompass two SRC1 molecules compared with the CAR(tcp):RXR·SRC1, which binds only a single SRC1. Moreover, sedimentation coefficients and molecular weights determined by analytical ultracentrifugation confirm the SAXS model. Cell-based transcription assays show that disrupting the SRC1 binding site on RXR alters the transactivation by CAR:RXR. These data suggest a broader role for RXR within heterodimers, whereas offering multiple strategies for the assembly of the transcription complex.

SUBMITTER: Pavlin MR 

PROVIDER: S-EPMC4155646 | BioStudies | 2014-01-01

SECONDARY ACCESSION(S): 1XLS

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3548980 | BioStudies
2004-01-01 | S-EPMC424365 | BioStudies
2012-01-01 | S-EPMC3341017 | BioStudies
2011-01-01 | S-EPMC3032979 | BioStudies
2009-01-01 | S-EPMC2755658 | BioStudies
2007-01-01 | S-EPMC2518310 | BioStudies
2015-01-01 | S-EPMC5414759 | BioStudies
2012-09-05 | E-GEOD-39277 | ArrayExpress
2009-01-01 | S-EPMC2613208 | BioStudies
2001-01-01 | S-EPMC1222239 | BioStudies