PMID- 8387213
OWN - NLM
STAT- MEDLINE
DCOM- 19930601
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 90
IP  - 9
DP  - 1993 May 1
TI  - Efficient transactivation by retinoic acid receptors in yeast requires retinoid X 
      receptors.
PG  - 4281-5
AB  - All-trans and 9-cis retinoic acids are natural derivatives of vitamin A that 
      modulate gene expression as a consequence of binding to nuclear retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). RXRs form heterodimers with 
      RARs in vitro, and such complexes display enhanced binding affinities for cognate 
      DNA response elements. As yeast is devoid of endogenous RARs and RXRs, we used 
      this organism to investigate whether transactivation in vivo requires RAR/RXR 
      heterodimers. Using a domain-swapping approach, we demonstrate that chimeric RAR 
      alpha 1 and RXR alpha containing the DNA-binding domain of the estrogen receptor 
      activate transcription of a cognate reporter gene in yeast, independently of each 
      other. These activities result from an inducible transcription activation 
      function located in the ligand-binding domains of RAR alpha 1 and RXR alpha and a 
      constitutive activation function located in the A/B region of RAR alpha 1. The 
      inducible activation function of RXR alpha is induced exclusively by 
      9-cis-retinoic acid in this system. Transactivation of a reporter gene containing 
      a retinoic acid response element by RAR alpha was considerably increased by RXR 
      alpha, even in the absence of ligand. Optimal induction was achieved with 
      9-cis-retinoic acid, which stimulates the activity of both receptors. This study 
      illustrates the utility of yeast to investigate signal transduction by retinoids 
      in the absence of endogenous RARs, RXRs, and detectable retinoic acid 
      isomerization.
FAU - Heery, D M
AU  - Heery DM
AD  - Laboratoire de Genetique Moleculaire des Eucaryotes, Centre National de la 
      Recherche Scientifique, I'Institut National de la Sante et de la Recherche 
      Medicale, Strasbourg, France.
FAU - Zacharewski, T
AU  - Zacharewski T
FAU - Pierrat, B
AU  - Pierrat B
FAU - Gronemeyer, H
AU  - Gronemeyer H
FAU - Chambon, P
AU  - Chambon P
FAU - Losson, R
AU  - Losson R
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 (Codon)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
GS  - URA3
MH  - Animals
MH  - Base Sequence
MH  - Carrier Proteins/drug effects/*genetics/metabolism
MH  - Cloning, Molecular
MH  - Codon/genetics
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Genetic Vectors
MH  - Humans
MH  - Macromolecular Substances
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides
MH  - Plasmids
MH  - Promoter Regions, Genetic
MH  - Receptors, Cell Surface/drug effects/*genetics/metabolism
MH  - Receptors, Estrogen/genetics/metabolism
MH  - Receptors, Retinoic Acid
MH  - Recombinant Fusion Proteins/metabolism
MH  - Restriction Mapping
MH  - Retinoid X Receptors
MH  - Retinoids/metabolism
MH  - Saccharomyces cerevisiae/genetics/*metabolism
MH  - TATA Box
MH  - *Transcription Factors
MH  - Transcriptional Activation
MH  - Tretinoin/metabolism/*pharmacology
PMC - PMC46490
EDAT- 1993/05/01 00:00
MHDA- 1993/05/01 00:01
PMCR- 1993/11/01
CRDT- 1993/05/01 00:00
PHST- 1993/05/01 00:00 [pubmed]
PHST- 1993/05/01 00:01 [medline]
PHST- 1993/05/01 00:00 [entrez]
PHST- 1993/11/01 00:00 [pmc-release]
AID - 10.1073/pnas.90.9.4281 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1993 May 1;90(9):4281-5. doi: 10.1073/pnas.90.9.4281.