PMID- 8264595
OWN - NLM
STAT- MEDLINE
DCOM- 19940121
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 14
IP  - 1
DP  - 1994 Jan
TI  - Different agonist- and antagonist-induced conformational changes in retinoic acid 
      receptors analyzed by protease mapping.
PG  - 287-98
AB  - The pleiotropic effects of retinoic acid on cell differentiation and 
      proliferation are mediated by two subfamilies of nuclear receptors, the retinoic 
      acid receptors (RARs) and the retinoid X receptors (RXRs). Recently the synthetic 
      retinoid Ro 41-5253 was identified as a selective RAR alpha antagonist. As 
      demonstrated by gel retardation assays, Ro 41-5253 and two related new RAR alpha 
      antagonists do not influence RAR alpha/RXR alpha heterodimerization and DNA 
      binding. In a limited trypsin digestion assay, complexation of RAR alpha with 
      retinoic acid or several other agonistic retinoids altered the degradation of the 
      receptor such that a 30-kDa proteolytic fragment became resistant to proteolysis. 
      This suggests a ligand-induced conformational change, which may be necessary for 
      the interaction of the DNA-bound RAR alpha/RXR alpha heterodimer with other 
      transcription factors. Our results demonstrate that antagonists compete with 
      agonists for binding to RAR alpha and may induce a different structural 
      alteration, suggested by the tryptic resistance of a shorter 25-kDa protein 
      fragment in the digestion assay. This RAR alpha conformation seems to allow RAR 
      alpha/RXR alpha binding to DNA but not the subsequent transactivation of target 
      genes. Protease mapping with C-terminally truncated receptors revealed that the 
      proposed conformational changes mainly occur in the DE regions of RAR alpha. 
      Complexation of RAR beta, RAR gamma, and RXR alpha, as well as the vitamin D3 
      receptor, with their natural ligands resulted in a similar resistance of 
      fragments to proteolytic digestion. This could mean that ligand-induced 
      conformational changes are a general feature in the hormonal activation of 
      vitamin D3 and retinoid receptors.
FAU - Keidel, S
AU  - Keidel S
AD  - Department of Dermatology, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
FAU - LeMotte, P
AU  - LeMotte P
FAU - Apfel, C
AU  - Apfel C
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Benzoates)
RN  - 0 (Chromans)
RN  - 0 (Naphthalenes)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 144092-31-9 (Ro 41-5253)
RN  - 153049-51-5 (Ro 46-5471)
RN  - 153049-52-6 (Ro 46-8515)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Animals
MH  - Benzoates/pharmacology
MH  - Chromans/pharmacology
MH  - Cloning, Molecular
MH  - Endopeptidases
MH  - Humans
MH  - Mice
MH  - Models, Biological
MH  - Naphthalenes/pharmacology
MH  - Peptide Mapping
MH  - Protein Conformation/drug effects
MH  - Receptors, Cytoplasmic and Nuclear/*chemistry/drug effects/genetics
MH  - Receptors, Retinoic Acid/*chemistry/drug effects/genetics
MH  - Retinoid X Receptors
MH  - Retinoids/pharmacology
MH  - Sequence Deletion
MH  - *Transcription Factors
MH  - Tretinoin/pharmacology
PMC - PMC358378
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
PMCR- 1994/01/01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
PHST- 1994/01/01 00:00 [pmc-release]
AID - 10.1128/mcb.14.1.287-298.1994 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1994 Jan;14(1):287-98. doi: 10.1128/mcb.14.1.287-298.1994.