Abstract
Retinoic acid receptor-related orphan receptor (ROR) agonists have been shown to regulate circadian rhythms in cultured cells and to improve various disease outcomes in animal models. Because expression of the core nucleotide excision repair protein XPA is governed by the circadian clock, we examined whether a natural and synthetic ROR agonist (nobiletin and SR1078, respectively) impact XPA expression and cellular responses to UV radiation in human keratinocytes. Interestingly, though these compounds have little effect on total XPA expression, they both reduce the expression of the endopeptidase cathepsin L (CTSL), which is known to act on several nuclear proteins, including at the C-terminus of XPA under defined cell lysis conditions.
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