Document Detail

Dominant-negative retinoic acid receptors elicit epidermal defects through a non-canonical pathway.
MedLine Citation:
PMID:  15528198     Owner:  NLM     Status:  MEDLINE    
Previous work has shown that a dominant-negative retinoic acid receptor alpha (dnRARalpha), expressed under the K14 promoter, causes severe epidermal defects. Similar defects are, however, not seen in RARalphagamma double null mutant mice, which lack the entire complement of RARs expressed in the epidermis. To investigate the mechanism of action of these dominant-negative receptors, dnRARalpha or a DNA binding-deficient variant, dnRARalpha(DBD), were targeted to the basal epidermis. Expression of either receptor type led to similar epidermal phenotypes suggesting that both RAR mutants acted through a common mechanism. The epidermal phenotype was reminiscent of defects seen in p63(-/-) mice. Consistent with this, reduced p63 expression was observed in transgenic offspring expressing either RAR mutant, suggesting that down-regulation of p63 might underlie the effects of these receptors on epidermal development. By contrast, expression of p63 in the epidermis of RARalphagamma(-/-) offspring was unaffected, indicating that RARs were not essential for p63 expression. These findings suggest that dnRARs may impact on epidermal development through one or more non-canonical pathways, which are independent of receptor-DNA interaction.
Chang Feng Chen; David Lohnes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-24     Completed Date:  2005-03-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3012-21     Citation Subset:  IM    
Division of Experimental Medicine, Department of Medicine, McGill University, Montreal K1H 8M5, Canada.
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MeSH Terms
COS Cells
DNA / metabolism
DNA, Complementary / metabolism
Dose-Response Relationship, Drug
Epidermis / metabolism,  pathology*
Genes, Dominant
Keratinocytes / metabolism
Keratins / metabolism
Mice, Transgenic
Models, Genetic
Mutagenesis, Site-Directed
Phosphoproteins / genetics*
Promoter Regions, Genetic
Protein Binding
Receptors, Retinoic Acid / genetics*,  physiology*
Signal Transduction
Time Factors
Trans-Activators / genetics*
Reg. No./Substance:
0/DNA, Complementary; 0/Phosphoproteins; 0/Receptors, Retinoic Acid; 0/Trans-Activators; 0/Trp63 protein, mouse; 0/retinoic acid receptor alpha; 68238-35-7/Keratins; 9007-49-2/DNA

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