Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes
Language: 
English
Abstract: 

The ID (inhibitor of differentiation or DNA binding) helix-loop-helix proteins are important mediators of cellular differentiation and proliferation in a variety of cell types through regulation of gene expression. Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation. Our hypothesis is that the ID proteins are targets of the retinoic acid signaling pathway in keratinocytes. Retinoids, vitamin A analogues, are powerful regulators of cell growth and differentiation and are widely used in the prevention and treatment of a variety of cancers in humans. Furthermore, retinoic acid is necessary for the maintenance of epithelial differentiation and demonstrates an inhibitory action on skin carcinogenesis. We examined the effect of all-trans retinoic acid on expression of ID-1, -2, -3, and -4 in normal human keratinocytes and found that exposure of these cells to all-trans retinoic acid causes an increase in both ID-1 and ID-3 gene expression. Furthermore, our data show that this increase is mediated by increased transcription involving several cis-acting elements in the distal portion of the promoter, including a CREB-binding site, an Egr1 element, and an YY1 site. These data demonstrate that the ID proteins are direct targets of the retinoic acid signaling pathway. Given the importance of the ID proteins to epidermal differentiation, these results suggest that IDs may be mediating some of the effects of all-trans retinoic acid in normal human keratinocytes.

Author(s): 
Villano, C. M.
White, L. A.
Item Type: 
Journal Article
Publication Title: 
Toxicology and Applied Pharmacology
Journal Abbreviation: 
Toxicol. Appl. Pharmacol.
Publication Date: 
8/1/2006
Publication Year: 
2006
Pages: 
219-229
Volume: 
214
Issue: 
3
ISSN: 
0041-008X
DOI: 
10.1016/j.taap.2005.12.015
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 16494909

Turabian/Chicago Citation

C. M. Villano and L. A. White. 8/1/2006. "Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes." Toxicology and Applied Pharmacology 214: 3: 219-229. 10.1016/j.taap.2005.12.015.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.taap.2005.12.015 | issn = 0041-008X | volume = 214 | pages = 219-229 | last = Villano | first = C. M. | coauthors = White, L. A. | title = Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes | journal = Toxicology and Applied Pharmacology | date = 8/1/2006 | pmid = | pmc = }} </ref>