Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
29947 | Journal of Photochemistry and Photobiology B: Biology | 2014 | 8 Pages |
•A huCOP1 silenced transgenic keratinocyte cell line has been established.•The residual huCOP1 level was further reduced by UVB.•The decreased huCOP1 level resulted in more pronounced UVB induced gene expression.•HuCOP1 contributes to the downregulation of an UVB inducible transcriptional network.•HuCOP1 might operate by modifying the function of upstream regulators of the network.
Ultraviolet (UV) B is the most prominent physical carcinogen in the environment leading to the development of various skin cancers. We have previously demonstrated that the human ortholog of the Arabidopsis thaliana constitutive photomorphogenesis 1 (COP1) protein, huCOP1, is expressed in keratinocytes in a UVB-regulated manner and is a negative regulator of p53 as a posttranslational modifier. However, it was not known whether huCOP1 plays a role in mediating the UVB-induced early transcriptional responses of human keratinocytes. In this study, we report that stable siRNA-mediated silencing of huCOP1 affects the UVB response of several genes within 2 h of irradiation, indicating that altered huCOP1 expression sensitizes the cells toward UVB. Pathway analysis identified a molecular network in which 13 of the 30 examined UVB-regulated genes were organized around three central proteins. Since the expression of the investigated genes was upregulated by UVB in the siCOP1 cell line, we hypothesize that huCOP1 is a repressor of the identified pathway. Several members of the network have been implicated previously in the pathogenesis of non-melanoma skin cancers; therefore, clarifying the role of huCOP1 in these skin diseases may have clinical relevance in the future.