Retinoylation (retinoic acid acylation) is a covalent modification of proteins occurring in a variety of eukaryotic cell lines. In this study, we found that proteins in undifferentiated and squamous-differentiated normal human epidermal keratinocytes were retinoylated after treatment with [3H]retinoic acid. The major retinoylated proteins were identified as cytokeratins based on their profile in two-dimensional gel electrophoresis and their immunoreactivity with anti-keratin monoclonal antibodies. The covalently bound [3H]retinoic acid was not removed by mild hydrolysis with methanolic-KOH indicating that it is not linked to the cytokeratins by a thioester bond. The results raise the possibility that retinoylation of cytokeratins is involved in some of the effects of retinoic acid on keratinocytes.
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