Regulation of gli activity by all-trans retinoic acid in mouse keratinocytes.
Sonic hedgehog (Shh) signaling is essential for many normal developmental processes. The Shh signal is interpreted by the Gli transcription factors. Elevated Gli-1 expression has been associated with several neoplasms, including basal cell carcinoma. All-trans retinoic acid (RA) has strong effects on epidermal growth and differentiation and has been used for the treatment of various epithelial disorders. In this report, we show that RA can inhibit Gli activity in immortalized murine keratinocytes in a RA receptor-specific manner. This inhibition may occur, at least in part, through sequestration of the transcriptional coactivator cyclic AMP-responsive element-binding protein-binding protein and suggests a novel effect of retinoid excess on Shh signaling.
Goyette
P
P
Department of Molecular Biology, Université de Montréal, Quebec, Canada.
Allan
D
D
Peschard
P
P
Chen
C F
CF
Wang
W
W
Lohnes
D
D
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D053823:Hedgehog Proteins; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000494:pharmacology; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000502:physiology; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
D016588:Anticarcinogenic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C082593:GLI2 protein, human; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D014212:Tretinoin