Document Detail


Dominant-negative retinoic acid receptors elicit epidermal defects through a non-canonical pathway.
MedLine Citation:
PMID:  15528198     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Chang Feng Chen; David Lohnes
Related Documents :
8798398 - Altered transforming growth factor signaling in epithelial cells when ras activation is...
1497868 - Localization of ras proto-oncogene expression during development in xenopus laevis.
23676118 - Alternative in vitro approach for assessing ahr-mediated cyp1a induction by dioxins in ...
17594488 - Constitutive upregulation of the transforming growth factor-beta pathway in rheumatoid ...
22469988 - Mir-143 regulates hexokinase 2 expression in cancer cells.
25296958 - Anti-inflammatory effects of propofol on lipopolysaccharides-treated rat hepatic kupffe...
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    
Affiliation:
Division of Experimental Medicine, Department of Medicine, McGill University, Montreal K1H 8M5, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
COS Cells
DNA / metabolism
DNA, Complementary / metabolism
Dose-Response Relationship, Drug
Down-Regulation
Epidermis / metabolism,  pathology*
Genes, Dominant
Immunohistochemistry
Keratinocytes / metabolism
Keratins / metabolism
Mice
Mice, Transgenic
Models, Genetic
Mutagenesis, Site-Directed
Mutation
Phenotype
Phosphoproteins / genetics*
Promoter Regions, Genetic
Protein Binding
Receptors, Retinoic Acid / genetics*,  physiology*
Signal Transduction
Time Factors
Trans-Activators / genetics*
Transfection
Transgenes
Chemical
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Corl1, a novel neuronal lineage-specific transcriptional corepressor for the homeodomain transcripti...
Next Document:  Altered interaction and expression of proteins involved in neurosecretion in scrapie-infected GT1-1 ...