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  • The EMBO Journal (2005) 24, 128 - 137
  • doi:10.1038/sj.emboj.7600501

Published online: 16 December 2004

NF-kappaB/Egr-1/Gadd45 are sequentially activated upon UVB irradiation to mediate epidermal cell death

Raphaël Thyss1, Virginie Virolle1, Véronique Imbert2, Jean-François Peyron2, Daniel Aberdam1 and Thierry Virolle1,3

  1. INSERM U634 Biologie et Physiopathologie Cutanée, UFR de Médecine, Nice, France
  2. INSERM U526 Activation des cellules Hématopoïétiques, Physiopathologie de la survie et de la mort cellulaires et infection virale, UFR de Médecine, Nice, France
  3. Present address: UMR 1112, ROSE 400, Routes des Chappes, BP 167, 06903 Sophia Antipolis Cedex, France

Correspondence to:

Thierry Virolle, INSERM U634 Biologie et Physiopathologie Cutanée, UFR de Médecine, Avenue de Valombrose, 06107 Nice Cedex 2, France. Tel.: +33 4 92 38 6561; E-mail: virolle@unice.fr

Received 19 July 2004; Accepted 10 November 2004

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-kappaB and Egr-1 expression drastically inhibits UVB-mediated cell death. Furthermore, we demonstrate that Egr-1 is induced upon UVB irradiation through NF-kappaB 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-kappaB, 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.

  • Keywords:

    • apoptosis,
    • Egr-1,
    • Gadd45,
    • NF-kappaB,
    • UVB