PMID- 1324421
OWN - NLM
STAT- MEDLINE
DCOM- 19920924
LR  - 20131121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 6
IP  - 7
DP  - 1992 Jul
TI  - Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid 
      signaling specificities.
PG  - 1153-62
AB  - Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) have been 
      shown to interact with nuclear auxiliary proteins resulting in heteromeric 
      complexes that bind strongly to their responsive elements. Recently the retinoid 
      X receptors (RXRs) have been identified as one class of these nuclear proteins. 
      RXRs strongly increase binding of TRs and RARs to a synthetic thyroid hormone 
      (and retinoic acid) responsive element. Here results show that the binding of the 
      heteromeric complexes to various natural response elements is highly specific and 
      dictated by the partner of RXR in the complex. TR alpha and TR beta formed 
      complexes with RXR alpha that strongly and selectively bound to natural thyroid 
      hormone responsive elements, i.e. those from the rat alpha-myosin heavy chain 
      gene and the rat malic enzyme gene. RXR alpha complexes with RAR alpha, RAR beta, 
      and RAR gamma bound selectively to retinoic acid responsive elements from the 
      human RAR beta 2 gene (hRAR beta 2), the gene of the rat cellular retinol binding 
      protein I and the human apolipoprotein A1 gene. Under the conditions used here 
      RXR alpha by itself did not bind to any of the responsive elements tested. 
      Although TRs and RARs formed heterodimers with RXR in solution, these complexes 
      were strongly stabilized by specific, high affinity response elements, but not by 
      low affinity response elements. Transfection analyses showed strong synergism 
      between receptors that formed effective heterodimers in transcriptional 
      activation on several but not all response elements. Overall, these data 
      demonstrate that RARs and TRs are unlikely to function as monomers or homodimers 
      on the response elements investigated here and require RXRs or comparable 
      proteins for effective response element activation.
FAU - Hermann, T
AU  - Hermann T
AD  - Cancer Research Center, La Jolla Cancer Research Foundation, California 92037.
FAU - Hoffmann, B
AU  - Hoffmann B
FAU - Zhang, X K
AU  - Zhang XK
FAU - Tran, P
AU  - Tran P
FAU - Pfahl, M
AU  - Pfahl M
LA  - eng
GR  - CA-50676/CA/NCI NIH HHS/United States
GR  - CA-519931/CA/NCI NIH HHS/United States
GR  - DK-35083/DK/NIDDK 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 Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Carrier Proteins/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/*metabolism
MH  - Protein Binding
MH  - Protein Multimerization
MH  - Rats
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, Retinoic Acid
MH  - Receptors, Thyroid Hormone/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Retinoid X Receptors
MH  - *Signal Transduction
MH  - *Transcription Factors
MH  - Transcription, Genetic
MH  - Transcriptional Activation
MH  - Tretinoin/*metabolism
MH  - Triiodothyronine/*metabolism
EDAT- 1992/07/01 00:00
MHDA- 1992/07/01 00:01
CRDT- 1992/07/01 00:00
PHST- 1992/07/01 00:00 [pubmed]
PHST- 1992/07/01 00:01 [medline]
PHST- 1992/07/01 00:00 [entrez]
AID - 10.1210/mend.6.7.1324421 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1992 Jul;6(7):1153-62. doi: 10.1210/mend.6.7.1324421.