PMID- 7935766
OWN - NLM
STAT- MEDLINE
DCOM- 19941031
LR  - 20061115
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 371
IP  - 6497
DP  - 1994 Oct 6
TI  - Regulation of retinoid signalling by receptor polarity and allosteric control of 
      ligand binding.
PG  - 528-31
AB  - Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) regulate 
      transcription by binding to response elements in target genes that generally 
      consist of two direct repeat half-sites of consensus sequence AGGTCA (ref. 1). 
      RAR/RXR heterodimers activate transcription in response to all-trans or 9-cis 
      retinoic acid by binding to direct repeats spaced by five base pairs (DR5 
      elements), such that RAR occupies the downstream half-site. RXR homodimers 
      activate transcription in response to 9-cis retinoic acid by binding to direct 
      repeats spaced by one base pair (DR1 elements). Although RXR/RAR heterodimers 
      bind to DR1 elements with higher affinity than RXR homodimers, in most contexts 
      they are unable to activate transcription in response to either all-trans or 
      9-cis retinoic acid. As a result, RARs inhibit RXR-dependent transcription from 
      these sites. We report that the switching of the RAR from an activator to an 
      inhibitor of retinoid-dependent transcription requires that it be bound to the 
      upstream half-site of DR1 elements and that it allosterically block the binding 
      of ligand to the RXR.
FAU - Kurokawa, R
AU  - Kurokawa R
AD  - Division of Cellular and Molecular Medicine, University of California, San Diego 
      92093-0656.
FAU - DiRenzo, J
AU  - DiRenzo J
FAU - Boehm, M
AU  - Boehm M
FAU - Sugarman, J
AU  - Sugarman J
FAU - Gloss, B
AU  - Gloss B
FAU - Rosenfeld, M G
AU  - Rosenfeld MG
FAU - Heyman, R A
AU  - Heyman RA
FAU - Glass, C K
AU  - Glass CK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Allosteric Regulation
MH  - Base Sequence
MH  - Cell Line
MH  - DNA/metabolism
MH  - Escherichia coli
MH  - Humans
MH  - Ligands
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Repetitive Sequences, Nucleic Acid
MH  - Retinoid X Receptors
MH  - *Signal Transduction
MH  - *Transcription Factors
MH  - *Transcription, Genetic
EDAT- 1994/10/06 00:00
MHDA- 1994/10/06 00:01
CRDT- 1994/10/06 00:00
PHST- 1994/10/06 00:00 [pubmed]
PHST- 1994/10/06 00:01 [medline]
PHST- 1994/10/06 00:00 [entrez]
AID - 10.1038/371528a0 [doi]
PST - ppublish
SO  - Nature. 1994 Oct 6;371(6497):528-31. doi: 10.1038/371528a0.