Résumé
Increased gene expression as a consequence of environmental stress is typically observed in mammalian cells. In the past few years the
cis-and
trans-acting genetic elements responsible for gene induction by radiation (from UV-C to visible light) started to be well characterized. The molecular mechanisms involved in the cell response to radiation reveal that an important control occurs at the transcriptional level and is coordinated by various transcription factors. Among these transcription factors, the well-known Rel/NF-kB family of vertebrate transcription factors plays a pivotal role as it controls both the inflammatory and immune responses. The NF-kB family comprises a number of structurally related, interacting proteins that bind DNA as dimers and whose activity is regulated by subcellular location. This family includes many members (p50, p52, RelA, RelB, c-Rel,…), most of which can form DNA-binding homoor heterodimers. Nuclear expression and consequent biological action of the eukaryotic NF-κB transcription factor complex are tightly regulated through its cytoplasmic retention by ankyrin-rich inhibitory proteins known as iκb. In the best-characterized example, IκB-α interacts with a p50/RelA (NF-κB) heterodimer to retain the complex in the cytoplasm and inhibit its DNA-binding activity. Upon receiving a variety of signals, many of which are probably mediated by the generation of reactive oxygen species (ROS), IκB-α undergoes phosphorylation, is then ubiquitinated at nearby lysine residues and finally degraded by the proteasome, while still complexed with NF-κB. Removal of iκb-α uncovers the nuclear localization signals on subunits of NF-κB, allowing the complex to enter the nucleus, bind to DNA and affect gene expression. In this paper, we shall show that molecular mechanisms leading to NF-κB activation by UV or by photosensitization are initiated by oxidative damage at the membrane level or by the induction of DNA alterations. While the exact nature of the transduction intermediates is still unknown, we shall show that NF-κB activation by radiation follows different pathways from those used by pro-inflammatory cytokines.