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

Paper ID Volume ID Publish Year Pages File Format Full-Text
29947 44448 2014 8 PDF Available
Title
UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes
Abstract

•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.

Keywords
Constitutive photomorphogenic protein 1; Photobiology; UVB; Transcriptional regulation; Keratinocyte
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UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 140, November 2014, Pages 215–222
Authors
, , , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us