504 UVB-induced expression of fast-responding genes is modulated by huCOP1 in keratinocytes

Fazekas, Barbara and Polyánka, Hilda and Tax, Gábor and Szabó, Kornélia and Farkas, Katalin and Kinyó, Ágnes and Nagy, Ferenc and Kemény, Lajos and Széll, Márta and Ádám, Éva (2014) 504 UVB-induced expression of fast-responding genes is modulated by huCOP1 in keratinocytes. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 134 (S2). S89. ISSN 0022-202X

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Abstract

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. To clarify this question we produced transgenic cell lines in which the expression of huCOP1 was stably silenced. Real-time RT-PCR array showed that the 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.

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