PMID- 7852392
OWN - NLM
STAT- MEDLINE
DCOM- 19950315
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 7
DP  - 1995 Feb 17
TI  - Similar ligand-induced conformational changes of thyroid hormone receptors 
      regulate homo- and heterodimeric functions.
PG  - 3107-14
AB  - Thyroid hormone receptors (TRs) bind specific thyroid hormone response elements 
      (TREs) as heterodimers with retinoid X receptors (RXRs) and act as 
      transcriptional activators. As homodimers, TRs can bind a distinct set of 
      sequences and function as ligand sensitive repressors. In our study, we compared 
      the natural malic enzyme TRE (ME-TRE) as a model system for the TR/RXR 
      heterodimer pathway to the chicken lysozyme silencer element F2-TRE which is 
      strongly bound and regulated by TR/TR homodimers. Using electrophoretic mobility 
      shift assays, transient transfections with a variety of natural and synthetic 
      triiodothyronine and thyroxine derivatives as well as limited proteolytic 
      analysis, we show that the natural homo- and heterodimeric pathways show similar 
      ligand requirements. Furthermore, we observe that the ligand-induced 
      conformational changes in the receptor proteins that either result in a loss of 
      TR/TR homodimer binding and release of transcriptional repression or in 
      transcriptional activation of TR/RXR heterodimers are indistinguishable. 
      Therefore, we propose that in TR/TR homodimers and TR/RXR heterodimers very 
      similar moieties of the receptors are involved in ligand binding and subsequent 
      conformational changes that lead to loss of gene repression (TR/TR homodimer) and 
      gain of gene activation (TR/RXR heterodimer).
FAU - Bendik, I
AU  - Bendik I
AD  - Cancer Center, La Jolla Cancer Research Foundation, California 92037.
FAU - Pfahl, M
AU  - Pfahl M
LA  - eng
GR  - DK 35083/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Macromolecular Substances)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - EC 1.1.1.37 (Malate Dehydrogenase)
RN  - EC 1.1.1.39 (malate dehydrogenase (decarboxylating))
RN  - EC 3.2.1.17 (Muramidase)
RN  - Q51BO43MG4 (Thyroxine)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Chickens
MH  - Chlorocebus aethiops
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression/drug effects
MH  - Kidney
MH  - Kinetics
MH  - Macromolecular Substances
MH  - Malate Dehydrogenase/biosynthesis/metabolism
MH  - Molecular Sequence Data
MH  - Muramidase/genetics
MH  - Oligodeoxyribonucleotides
MH  - Receptors, Retinoic Acid/chemistry/metabolism
MH  - Receptors, Thyroid Hormone/*chemistry/*metabolism
MH  - Recombinant Fusion Proteins/chemistry/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Retinoid X Receptors
MH  - Structure-Activity Relationship
MH  - TATA Box
MH  - Thyroxine/analogs & derivatives/pharmacology
MH  - Transcription Factors/chemistry/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Triiodothyronine/analogs & derivatives/pharmacology
EDAT- 1995/02/17 00:00
MHDA- 1995/02/17 00:01
CRDT- 1995/02/17 00:00
PHST- 1995/02/17 00:00 [pubmed]
PHST- 1995/02/17 00:01 [medline]
PHST- 1995/02/17 00:00 [entrez]
AID - S0021-9258(18)82898-8 [pii]
AID - 10.1074/jbc.270.7.3107 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Feb 17;270(7):3107-14. doi: 10.1074/jbc.270.7.3107.