Cytokeratins 16 and 10 bind to retinoic acid covalently in skin tissue of mice

BACKGROUND: Retinoic acid (RA) has various biological effects in mammalian cells and tissues. In epidermal cells, RA is an inhibitor of differentiation to the squamous phenotype. The molecular mechanisms underlying the effects of RA on epidermal cells and other cell types are mediated by RA nuclear receptors and retinoylation (acylation by RA) of proteins. OBJECTIVES: To understand the components responsible for RA effects via RA nuclear receptors and retinoylation. METHODS: We examined for the first time RA-binding proteins in mouse skin in vivo by immunoblotting using anti-RA monoclonal antibodies and identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. RESULTS: We identified eight RA-binding proteins in the skin of hairless mice that were increased by topical RA treatment. Three of these proteins were identified as cytokeratin 10, cytokeratin 16 and serum albumin. CONCLUSION: These results raise the possibility that RA binding to cytokeratins in vivo may be involved in the effect of RA on keratinocytes in mouse skin.