Down-regulation of p63 is required for epidermal UV-B-induced apoptosis

In the epidermis, p53 plays an important role in UV-B protection that Led u s to examine the role, if any, that p63, a p53 homologue highly expressed i n the basal layer of the epidermis, might play in the epidermal UV-B respon se. One p63 isoform, Delta Np63 alpha, decreased dramatically in normal ker atinocytes or newborn epidermis at both the protein and RNA levels after UV -B irradiation. In an attempt to further investigate the significance of th e UV-B-induced decrease of this p63 isoform as well as further delineate th e function of p63 in the epidermis, we generated transgenic mice that const itutively express Delta Np63 alpha in the mouse epidermis using the loricri n promoter (ML.Delta Np63 alpha). The ML.Delta Np63 alpha mouse epidermis d eveloped normally, with no overt phenotype and an unaltered proliferation r ate. When challenged by UV-B exposure, the ML.Delta Np63 alpha mice exhibit ed a 40-45% decrease in the number of apoptotic cells in the epidermis as c ompared with nontransgenic littermates. These results suggest that aberrant expression of Delta Np63 alpha altered the UV-B-induced apoptotic pathway in the transgenic epidermis, proving that down-regulation of Delta Np63 alp ha in response to UV-B is important to epidermal apoptosis. The forced over expression of Delta Np63 alpha may act via a dominant negative effect on th e endogenous p53 transcriptional activity required for UV-B-induced apoptos is.