PMID- 8524299
OWN - NLM
STAT- MEDLINE
DCOM- 19960119
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 16
IP  - 1
DP  - 1996 Jan
TI  - A shift in the ligand responsiveness of thyroid hormone receptor alpha induced by 
      heterodimerization with retinoid X receptor alpha.
PG  - 219-27
AB  - Thyroid hormone (T3) receptors (T3Rs) are ligand-modulated transcription factors 
      that bind to thyroid hormone response elements (T3REs) and mediate either 
      positive or negative transcriptional regulation of target genes. In addition, in 
      response to ligand binding, T3Rs can interfere with AP-1 activity and thereby 
      inhibit transcription of AP-1-responsive genes. T3Rs were recently shown to form 
      heterodimers with retinoid X receptors (RXRs), leading to increased binding to 
      T3REs in vitro and potentiation of transcriptional responses in vivo. Here we 
      demonstrate that T3R alpha forms stable heterodimers with RXR alpha in living 
      cells. Most important, we describe a new role for RXR alpha in modulating 
      ligand-dependent T3R alpha activity: heterodimerization with RXR alpha greatly 
      increases transcriptional interference with AP-1 activity, augments T3-dependent 
      transcriptional activation, and potentiates the reversal of ligand-independent 
      activation by T3R alpha. In all three cases, the responses occur at substantially 
      lower T3 concentrations when elicited by T3R alpha plus RXR alpha than by T3R 
      alpha alone. In vitro, the binding of T3 decreases the DNA-binding activity of 
      T3R alpha homodimers but does not affect DNA binding by T3R alpha:RXR alpha 
      heterodimers. We provide evidence that increased activities of T3R alpha at lower 
      T3 concentrations are not due to changes in its T3 binding properties. Instead, 
      the altered response could be mediated by either RXR alpha-induced conformational 
      changes, increased stability of heterodimers over homodimers, especially 
      following T3 binding, or both.
FAU - Claret, F X
AU  - Claret FX
AD  - Department of Pharmacology, School of Medicine, University of California, San 
      Diego, La Jolla 92093-0636, USA.
FAU - Antakly, T
AU  - Antakly T
FAU - Karin, M
AU  - Karin M
FAU - Saatcioglu, F
AU  - Saatcioglu F
LA  - eng
GR  - CA50528/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Ligands)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - DNA/metabolism
MH  - Humans
MH  - Ligands
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Receptors, Retinoic Acid/chemistry/genetics/*metabolism
MH  - Receptors, Thyroid Hormone/chemistry/genetics/*metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factor AP-1/metabolism
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - Transcriptional Activation
MH  - Triiodothyronine/metabolism
PMC - PMC230995
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
PMCR- 1996/01/01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
PHST- 1996/01/01 00:00 [pmc-release]
AID - 10.1128/MCB.16.1.219 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1996 Jan;16(1):219-27. doi: 10.1128/MCB.16.1.219.