The specific activation of gadd45 following UVB radiation requires the POUfamily gene product N-oct3 in human melanoma cells

Here we report the specific regulation of gadd45 expression in human melano ma cell lines following UVB radiation. This solar wavelength is likely to b e involved in melanoma aetiology. We have previously shown that gadd45 expr ession is strongly enhanced in a p53-independent manner following UVB irrad iation, unlike the other p53 target genes studied. Furthermore, gadd45 is s pecifically activated in melanocytes since its induction in response to UVB , is not observed in other skin cells such as keratinocytes or fibroblasts. To investigate this particular regulation of gadd45, we analysed the UVB-i nduced response of different gadd45 promoter regions. Thus, a minimal promo ter region of 50 bp length, responsible for gadd45 activation in melanoma c ell lines following UVB irradiation, was determined. In electrophoretic mob ility shift assays (EMSAs), we showed that this region (-106/-56) of the ga dd45 promoter which contains two identical octamers, binds the POU family g ene products oct-l and N-oct3. Given the specific expression pattern of N-o ct3 in melanocyte, we invalidated the expression of this transcription fact or in melanoma cells: such an abrogation of N-oct3 protein expression in me lanoma cells impeded gadd45 UVB-response. Thus the response of melanocyte t o UVB may use an original and previously undescribed pathway.