PMID- 9121466
OWN - NLM
STAT- MEDLINE
DCOM- 19970424
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 17
IP  - 4
DP  - 1997 Apr
TI  - Peroxisome proliferator-activated receptors and retinoic acid receptors 
      differentially control the interactions of retinoid X receptor heterodimers with 
      ligands, coactivators, and corepressors.
PG  - 2166-76
AB  - As the obligate member of most nuclear receptor heterodimers, retinoid X 
      receptors (RXRs) can potentially perform two functions: cooperative binding to 
      hormone response elements and coordinate regulation of target genes by RXR 
      ligands. In this paper we describe allosteric interactions between RXR and two 
      heterodimeric partners, retinoic acid receptors (RARs) and peroxisome 
      proliferator-activated receptors (PPARs); RARs and PPARs prevent and permit 
      activation by RXR-specific ligands, respectively. By competing for dimerization 
      with RXR on response elements consisting of direct-repeat half-sites spaced by 1 
      bp (DR1 elements), the relative abundance of RAR and PPAR determines whether the 
      RXR signaling pathway will be functional. In contrast to RAR, which prevents the 
      binding of RXR ligands and recruits the nuclear receptor corepressor N-CoR, PPAR 
      permits the binding of SRC-1 in response to both RXR and PPAR ligands. 
      Overexpression of SRC-1 markedly potentiates ligand-dependent transcription by 
      PPARgamma, suggesting that SRC-1 serves as a coactivator in vivo. Remarkably, the 
      ability of RAR to both block the binding of ligands to RXR and interact with 
      corepressors requires the CoR box, a structural motif residing in the N-terminal 
      region of the RAR ligand binding domain. Mutations in the CoR box convert RAR 
      from a nonpermissive to a permissive partner of RXR signaling on DR1 elements. We 
      suggest that the differential recruitment of coactivators and corepressors by 
      RAR-RXR and PPAR-RXR heterodimers provides the basis for a transcriptional switch 
      that may be important in controlling complex programs of gene expression, such as 
      adipocyte differentiation.
FAU - DiRenzo, J
AU  - DiRenzo J
AD  - Department of Medicine, University of California, San Diego, La Jolla 92093-0651, 
      USA.
FAU - Soderstrom, M
AU  - Soderstrom M
FAU - Kurokawa, R
AU  - Kurokawa R
FAU - Ogliastro, M H
AU  - Ogliastro MH
FAU - Ricote, M
AU  - Ricote M
FAU - Ingrey, S
AU  - Ingrey S
FAU - Horlein, A
AU  - Horlein A
FAU - Rosenfeld, M G
AU  - Rosenfeld MG
FAU - Glass, C K
AU  - Glass CK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Cell Line
MH  - DNA/genetics/metabolism
MH  - Dimerization
MH  - Histone Acetyltransferases
MH  - Ligands
MH  - Mice
MH  - Microbodies/*metabolism
MH  - Models, Biological
MH  - Mutation
MH  - Nuclear Receptor Coactivator 1
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Receptors, Retinoic Acid/chemistry/genetics/*metabolism
MH  - Retinoid X Receptors
MH  - Signal Transduction
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - Transfection
PMC - PMC232065
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
PMCR- 1997/04/01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
PHST- 1997/04/01 00:00 [pmc-release]
AID - 10.1128/MCB.17.4.2166 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1997 Apr;17(4):2166-76. doi: 10.1128/MCB.17.4.2166.