Edinburgh Research Explorer

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

Research output: Contribution to journalArticle

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

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)215-22
Number of pages8
JournalJournal of Photochemistry & Photobiology
Volume140
DOIs
StatePublished - Nov 2014

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.

    Research areas

  • Cell Line, Gene Expression Regulation, Gene Regulatory Networks, Gene Silencing, Humans, Keratinocytes, RNA, Small Interfering, Time Factors, Transcription, Genetic, Ubiquitin-Protein Ligases, Ultraviolet Rays

ID: 21667371