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NF‐κB/Egr‐1/Gadd45 are sequentially activated upon UVB irradiation to mediate epidermal cell death
Author(s) -
Thyss Raphaël,
Virolle Virginie,
Imbert Véronique,
Peyron JeanFrançois,
Aberdam Daniel,
Virolle Thierry
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600501
Subject(s) - medicine , microbiology and biotechnology , biology
Chronic sun exposure can lead to severe skin disorders such as carcinogenesis. The cell death process triggered by ultraviolet B (UVB) irradiation is crucial because it protects the surrounding tissue from the emergence and the accumulation of cells that bear the risk of becoming transformed. Here, we show that repression of NF‐κB and Egr‐1 expression drastically inhibits UVB‐mediated cell death. Furthermore, we demonstrate that Egr‐1 is induced upon UVB irradiation through NF‐κB activation and the binding of p65/RelA within the Egr‐1 promoter. We show that Egr‐1 contributes to the regulation of the Gadd45a and Gadd45b genes, which are involved in the control of cell cycle, DNA repair and apoptosis, by direct binding to their promoter. Our study demonstrates for the first time a signaling cascade involving sequential activation of NF‐κB, Egr‐1 and Gadd45 to induce UVB‐mediated cell death. Failure in the induction of each protagonist of this pathway alters the UVB‐mediated cell death process. Therefore, impairment of the cascade could be at the onset of skin carcinogenesis mediated by genotoxic stress.