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Regulation of Gli Activity by All-trans Retinoic Acid in Mouse Keratinocytes¹

Department of Molecular Biology, Université de Montréal [D. L.]; Division of Experimental Medicine, McGill University [D. A., C. F. C., D. L.]; and the Institut de Recherches Cliniques de Montréal [P. G., D. A., P. P., C. F. C., W. W., D. L.], Montréal, Québec, H2W 1R7 Canada

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 AMPresponsive element-binding protein-binding protein and suggests a novel effect of retinoid excess on Shh signaling.

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