UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes

B. Fazekas, H. Polyánka, A. Bebes, G. Tax, K. Szabó, K. Farkas, Á Kinyó, F. Nagy, L. Kemény, M. Széll, É Ádám

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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. 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.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalJournal of Photochemistry and Photobiology B: Biology
Volume140
DOIs
Publication statusPublished - Nov 2014

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Keywords

  • Constitutive photomorphogenic protein 1
  • Keratinocyte
  • Photobiology
  • Transcriptional regulation
  • UVB

ASJC Scopus subject areas

  • Radiation
  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging

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