title: UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes.
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. 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.
authors.affiliation: Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary. Electronic address: barbara.fazekas8@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Fazekas
authors.affiliation: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: H
authors.initials: H
authors.lastname: Polyánka
authors.affiliation: Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Bebes
authors.affiliation: Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Tax
authors.affiliation: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Szabó
authors.affiliation: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Farkas
authors.affiliation: Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Kinyó
authors.affiliation: Institute of Plant Biology, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: F
authors.initials: F
authors.lastname: Nagy
authors.affiliation: Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary; MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Kemény
authors.affiliation: MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary; Institute of Medical Genetics, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Széll
authors.affiliation: Institute of Plant Biology, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: É
authors.initials: É
authors.lastname: Ádám
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation / Q000528:radiation effects*; D053263:Gene Regulatory Networks / Q000528:radiation effects; D020868:Gene Silencing; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D034741:RNA, Small Interfering / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D034741:RNA, Small Interfering; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Constitutive photomorphogenic protein 1; Keratinocyte; Photobiology; Transcriptional regulation; UVB