PMID- 8380496
OWN - NLM
STAT- MEDLINE
DCOM- 19930208
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 90
IP  - 1
DP  - 1993 Jan 1
TI  - Retinoic acid receptors and retinoid X receptors: interactions with endogenous 
      retinoic acids.
PG  - 30-4
AB  - The binding of endogenous retinoids and stereoisomers of retinoic acid (RA) to 
      the retinoid nuclear receptors, RA receptor (RARs) and retinoid X receptors 
      (RXRs), was characterized using nucleosol preparations from transiently 
      transfected COS-1 cells. Among several stereoisomers of RA tested, including 
      7-cis-, 9-cis-, 11-cis-, 13-cis-, and all-trans-RA, only 9-cis-RA effectively 
      competes with 9-cis-[3H]RA binding to the RXRs. Additionally, the endogenous 
      retinoid trans-didehydro-RA (t-ddRA) does not interact with RXRs, whereas the 
      9-cis form of ddRA competes effectively. RXRs (alpha, beta, and gamma) bind 
      9-cis-RA with dissociation constants (Kd) of 15.7, 18.3, and 14.1 nM, 
      respectively. In contrast to the selectivity of RXRs for 9-cis-RA, RARs bind both 
      t-RA and 9-cis-RA with high affinity, exhibiting Kd values in the 0.2-0.7 nM 
      range for both ligands. Unlike RARs, the cellular RA binding proteins CRABPI or 
      CRABPII bind t-RA but do not bind 9-cis-RA. Consistent with the binding data, 
      9-cis-RA and 9-cis-ddRA transcriptionally activate both GAL4-RXR and GAL4-RAR 
      chimeric receptors with EC50 values of 3-20 nM for 9-cis-RA and 9-cis-ddRA, 
      whereas t-RA and t-ddRA efficiently activate only GAL4-RAR chimeric receptors. 
      Thus, 9-cis forms of endogenous retinoids can contribute to the pleiotropic 
      effects of retinoids by interacting with both the RARs and RXRs.
FAU - Allenby, G
AU  - Allenby G
AD  - Department of Toxicology and Pathology, Hoffmann-La Roche, Nutley, NJ 07110.
FAU - Bocquel, M T
AU  - Bocquel MT
FAU - Saunders, M
AU  - Saunders M
FAU - Kazmer, S
AU  - Kazmer S
FAU - Speck, J
AU  - Speck J
FAU - Rosenberger, M
AU  - Rosenberger M
FAU - Lovey, A
AU  - Lovey A
FAU - Kastner, P
AU  - Kastner P
FAU - Grippo, J F
AU  - Grippo JF
FAU - Chambon, P
AU  - Chambon P
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (GAL4 protein, S cerevisiae)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cytosol/metabolism
MH  - DNA-Binding Proteins
MH  - Fungal Proteins/genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Kinetics
MH  - Mice
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Receptors, Retinoic Acid
MH  - Recombinant Fusion Proteins/metabolism
MH  - Retinoid X Receptors
MH  - *Saccharomyces cerevisiae Proteins
MH  - *Transcription Factors
MH  - Transfection
MH  - Tretinoin/*metabolism
PMC - PMC45593
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
PMCR- 1993/07/01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
PHST- 1993/07/01 00:00 [pmc-release]
AID - 10.1073/pnas.90.1.30 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4. doi: 10.1073/pnas.90.1.30.