PMID- 26148973
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20181202
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 29
IP  - 10
DP  - 2015 Oct
TI  - Selective ligand activity at Nur/retinoid X receptor complexes revealed by 
      dimer-specific bioluminescence resonance energy transfer-based sensors.
PG  - 4256-67
LID - 10.1096/fj.14-259804 [doi]
AB  - Retinoid X receptors (RXRs) play a role as master regulators because of their 
      capacity to form heterodimers with other nuclear receptors (NRs). Accordingly, 
      retinoid signaling is involved in multiple biologic processes, including 
      development, cell differentiation, metabolism, and cell death. However, the role 
      and function of RXRs in different heterodimer complexes remain unidentified, 
      mainly because most RXR drugs (called rexinoids) are not selective of specific 
      heterodimer complexes. The lack of selectivity strongly limits the use of 
      rexinoids for specific therapeutic approaches. To better characterize rexinoids 
      at specific NR complexes, we have developed and optimized luciferase (Luc) 
      protein complementation(PCA)-based bioluminescence resonance energy transfer 
      (BRET) assays that can directly measure recruitment of a coactivator (CoA) motif 
      fused to yellow fluorescent protein (YFP) by specific NR dimers. To validate the 
      assays, we compared rexinoid modulation of CoA recruitment by the RXR homodimer 
      and by the heterodimers Nur77/RXR and Nurr1/RXR. Results revealed that some 
      rexinoids display selective CoA recruitment activities with homo- or heterodimer 
      complexes. In particular, SR11237 (BMS649) has stronger potency for recruitment 
      of CoA motif and transcriptional activity with the heterodimer Nur77/RXR than 
      other complexes. This technology should be useful in identifying new compounds 
      with specificity for individual dimeric species formed by NRs.
CI  - (c) FASEB.
FAU - Giner, Xavier C
AU  - Giner XC
AD  - *Faculte de Pharmacie and Groupe de Recherche Universitaire sur le Medicament, 
      and Institut de Recherche en Immunologie et Cancerologie, Universite de Montreal, 
      Montreal, Quebec, Canada.
FAU - Cotnoir-White, David
AU  - Cotnoir-White D
AD  - *Faculte de Pharmacie and Groupe de Recherche Universitaire sur le Medicament, 
      and Institut de Recherche en Immunologie et Cancerologie, Universite de Montreal, 
      Montreal, Quebec, Canada.
FAU - Mader, Sylvie
AU  - Mader S
AD  - *Faculte de Pharmacie and Groupe de Recherche Universitaire sur le Medicament, 
      and Institut de Recherche en Immunologie et Cancerologie, Universite de Montreal, 
      Montreal, Quebec, Canada.
FAU - Levesque, Daniel
AU  - Levesque D
AD  - *Faculte de Pharmacie and Groupe de Recherche Universitaire sur le Medicament, 
      and Institut de Recherche en Immunologie et Cancerologie, Universite de Montreal, 
      Montreal, Quebec, Canada daniel.levesque.1@umontreal.ca.
LA  - eng
GR  - 130407-1/Canadian Institutes of Health Research/Canada
GR  - MOP125863/Canadian Institutes of Health Research/Canada
GR  - MOP130407/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150706
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Bacterial Proteins)
RN  - 0 (Benzoates)
RN  - 0 (Ligands)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NR4A1 protein, human)
RN  - 0 (Nuclear Receptor Coactivators)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2)
RN  - 0 (Retinoid X Receptor gamma)
RN  - 0 (Retinoids)
RN  - 0 (yellow fluorescent protein, Bacteria)
RN  - 146670-40-8 (SR 11237)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Amino Acid Motifs/genetics
MH  - Amino Acid Sequence
MH  - Bacterial Proteins/genetics/metabolism
MH  - Benzoates/pharmacology
MH  - Bioluminescence Resonance Energy Transfer Techniques/*methods
MH  - HEK293 Cells
MH  - Humans
MH  - Ligands
MH  - Luminescent Proteins/genetics/metabolism
MH  - Microscopy, Fluorescence
MH  - Models, Biological
MH  - Multiprotein Complexes/chemistry/metabolism
MH  - Nuclear Receptor Coactivators/genetics/metabolism
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1/chemistry/genetics/*metabolism
MH  - Nuclear Receptor Subfamily 4, Group A, Member 2/chemistry/genetics/*metabolism
MH  - Protein Binding/drug effects
MH  - Protein Multimerization
MH  - Retinoid X Receptor gamma/chemistry/genetics/*metabolism
MH  - Retinoids/pharmacology
MH  - Tretinoin/pharmacology
PMC - PMC5346306
MID - CAMS6590
OTO - NOTNLM
OT  - cofactor recruitment
OT  - nuclear receptors
OT  - pharmacological parameters
OT  - protein conformation
OT  - receptor dimerization
COIS- Disclosure The authors declare no conflict of interest.
EDAT- 2015/07/08 06:00
MHDA- 2016/01/16 06:00
PMCR- 2017/03/11
CRDT- 2015/07/08 06:00
PHST- 2014/11/27 00:00 [received]
PHST- 2015/06/22 00:00 [accepted]
PHST- 2015/07/08 06:00 [entrez]
PHST- 2015/07/08 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
PHST- 2017/03/11 00:00 [pmc-release]
AID - fj.14-259804 [pii]
AID - 10.1096/fj.14-259804 [doi]
PST - ppublish
SO  - FASEB J. 2015 Oct;29(10):4256-67. doi: 10.1096/fj.14-259804. Epub 2015 Jul 6.