PMID- 25053412
OWN - NLM
STAT- MEDLINE
DCOM- 20150128
LR  - 20240321
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 289
IP  - 36
DP  - 2014 Sep 5
TI  - Agonist ligands mediate the transcriptional response of nuclear receptor 
      heterodimers through distinct stoichiometric assemblies with coactivators.
PG  - 24771-8
LID - 10.1074/jbc.M114.575423 [doi]
AB  - 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.
CI  - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Pavlin, Mark Remec
AU  - Pavlin MR
AD  - From the Department of Biochemistry, Cellular and Molecular Biology, The 
      University of Tennessee, Knoxville, Tennessee 37996 and.
FAU - Brunzelle, Joseph S
AU  - Brunzelle JS
AD  - the Department of Molecular Pharmacology and Biological Chemistry, Life Sciences 
      Collaborative Access Team, Northwestern University Feinberg School of Medicine, 
      Chicago, Illinois 60611.
FAU - Fernandez, Elias J
AU  - Fernandez EJ
AD  - From the Department of Biochemistry, Cellular and Molecular Biology, The 
      University of Tennessee, Knoxville, Tennessee 37996 and elias.fernandez@utk.edu.
LA  - eng
GR  - R56 DK097337/DK/NIDDK NIH HHS/United States
GR  - DK097337-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140722
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Constitutive Androstane Receptor)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retinoid X Receptor alpha)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Animals
MH  - Binding Sites/genetics
MH  - Cell Line
MH  - Constitutive Androstane Receptor
MH  - Humans
MH  - Ligands
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Weight
MH  - Mutation
MH  - Nuclear Receptor Coactivator 1/*chemistry/genetics/metabolism
MH  - Protein Binding
MH  - *Protein Multimerization
MH  - Protein Structure, Tertiary
MH  - Receptors, Cytoplasmic and Nuclear/*chemistry/genetics/metabolism
MH  - Retinoid X Receptor alpha/*chemistry/genetics/metabolism
MH  - Scattering, Small Angle
MH  - Transcriptional Activation
MH  - X-Ray Diffraction
PMC - PMC4155646
OTO - NOTNLM
OT  - Analytical Ultracentrifugation
OT  - Heterodimer
OT  - Nuclear Receptor
OT  - Protein Assembly
OT  - Small Angle X-ray Scattering (SAXS)
OT  - Stoichiometry
OT  - Transactivation
OT  - Transcription Coactivator
EDAT- 2014/07/24 06:00
MHDA- 2015/01/30 06:00
PMCR- 2015/09/05
CRDT- 2014/07/24 06:00
PHST- 2014/07/24 06:00 [entrez]
PHST- 2014/07/24 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
PHST- 2015/09/05 00:00 [pmc-release]
AID - S0021-9258(20)31633-1 [pii]
AID - M114.575423 [pii]
AID - 10.1074/jbc.M114.575423 [doi]
PST - ppublish
SO  - J Biol Chem. 2014 Sep 5;289(36):24771-8. doi: 10.1074/jbc.M114.575423. Epub 2014 
      Jul 22.