PMID- 8001825
OWN - NLM
STAT- MEDLINE
DCOM- 19950123
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 8
IP  - 24
DP  - 1994 Dec 15
TI  - Retinoid-dependent in vitro transcription mediated by the RXR/RAR heterodimer.
PG  - 3068-79
AB  - The effects of retinoids on gene regulation are mediated by retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). Here, we provide the first 
      biochemical evidence that, in vitro, ligand governs the transcriptional activity 
      of RXR alpha/RAR alpha by inducing conformational changes in the ligand-binding 
      domains. Using limited proteolytic digestion we show that binding of the cognate 
      ligand causes a conformational change in the carboxy-terminal part of the 
      receptor. We also show that recombinant RXR alpha/RAR alpha is partially active 
      in the absence of exogenously added ligand. Trans-activation depends critically 
      on the ligand-dependent transcriptional activation function AF-2 of RAR alpha. 
      Full activation by recombinant RXR alpha/RAR alpha, however, requires the 
      addition of either all-trans RA, 9-cis RA, or other RAR-specific agonists, 
      whereas an RAR alpha-specific antagonist abolishes trans-activation. 
      Intriguingly, the ligand-dependent AF-2 of RXR does not contribute to the level 
      of transcription from the RAR beta 2 promoter in vitro even when the cognate 
      ligand (9-cis RA) is bound. Thus, the major role of RXR in trans-activation of 
      the RAR beta 2 promoter is to serve as an auxiliary factor required for the 
      binding of RAR which, in turn, is directly responsible for transcriptional 
      activity.
FAU - Valcarcel, R
AU  - Valcarcel R
AD  - European Molecular Biology Laboratory (EMBL), Gene Expression Program, 
      Heidelberg, Germany.
FAU - Holz, H
AU  - Holz H
FAU - Jimenez, C G
AU  - Jimenez CG
FAU - Barettino, D
AU  - Barettino D
FAU - Stunnenberg, H G
AU  - Stunnenberg HG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
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
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Chromatography, Affinity
MH  - Gene Expression Regulation/*drug effects
MH  - Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/biosynthesis
MH  - Oligodeoxyribonucleotides
MH  - Promoter Regions, Genetic/drug effects
MH  - Protein Conformation/drug effects
MH  - Receptors, Retinoic Acid/*biosynthesis/chemistry/isolation & purification
MH  - Recombinant Fusion Proteins/biosynthesis/chemistry/isolation & purification
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - Transcription Factors/*biosynthesis/chemistry/isolation & purification
MH  - Transcription, Genetic/*drug effects
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tretinoin/pharmacology
MH  - Vaccinia virus
EDAT- 1994/12/15 00:00
MHDA- 1994/12/15 00:01
CRDT- 1994/12/15 00:00
PHST- 1994/12/15 00:00 [pubmed]
PHST- 1994/12/15 00:01 [medline]
PHST- 1994/12/15 00:00 [entrez]
AID - 10.1101/gad.8.24.3068 [doi]
PST - ppublish
SO  - Genes Dev. 1994 Dec 15;8(24):3068-79. doi: 10.1101/gad.8.24.3068.