Agonist ligands mediate the transcriptional response of nuclear receptor heterodimers through distinct stoichiometric assemblies with coactivators.
J Biol Chem
; 289(36): 24771-8, 2014 Sep 05.
Article
en En
| MEDLINE
| ID: mdl-25053412
ABSTRACT
The constitutive androstane (CAR) and retinoid X receptors (RXR) are ligand-mediated transcription factors of the nuclear receptor protein superfamily. Functional CARRXR 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 CARRXR, which distinctly bind two SRC1 molecules. We also observe that SRC1 transitions from a structurally plastic to a compact form upon binding CARRXR. 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 CARRXR. These data suggest a broader role for RXR within heterodimers, whereas offering multiple strategies for the assembly of the transcription complex.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores Citoplasmáticos y Nucleares
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Receptor alfa X Retinoide
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Multimerización de Proteína
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Coactivador 1 de Receptor Nuclear
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article