Regulation of Gli activity by all-trans retinoic acid in mouse keratinocytes

Sonic hedgehog (Shh) signaling is essential for many normal developmental p rocesses. The Shh signal is interpreted by the Gli transcription factors, E levated Gli-1 expression has been associated with several neoplasms, includ ing basal cell carcinoma. AU-trans retinoic acid (RA) has strong effects on epidermal growth and differentiation and has been used for the treatment o f various epithelial disorders. In this report, we show that RA can inhibit Gli activity in immortalized murine keratinocytes in a RA receptor-specifi c manner. This inhibition may occur, at Least in part, through sequestratio n of the transcriptional coactivator cyclic AMP-responsive element-binding protein-binding protein and suggests a novel effect of retinoid excess on S hh signaling.