Signaling pathways leading to transcription factors activation in response to UV-radiation

Signaling pathways leading to transcription factors activation in response to UV-radiation. UV-induced Nuclear Factor kappa B (NF-κB) pathway activation depends on phosphorylation of IκBα by Casein Kinase II (CK2) through the activation of p38-MAP kinase. Phosphorylation-induced degradation of IκBα releases NF-κB subunits RelA/p50, which enter into nucleus to activate gene transcription of targets genes. UV-induced phosphorylation of Eukaryotic Translation Initiation Factor 2α (eIF2α) inhibits de novo IκBα translation, whereas the existing IκBα is degraded, leading to NF-κB activation. The chemopreventive inhibition of NF-κB by natural compounds parthenolide and magnolol, as well as p38 blocking by (−)-Epigallocatechin 3-gallate (EGCG) is depicted. In AP-1 pathway, UV-induced activation of membrane receptors leads to the activation of MEKK, c-Jun NH2-Terminal Kinases (JNK), and p38. MAPKs phosphorylate transcription factors leading to increased expression of AP-1. In Nrf2 pathway, Nrf2 acts as a sensor for oxidative and electrophilic stress. In these conditions, phase 2 inducers cause the modification of Keap1 and/or phosphorylation of Nrf2 resulting in the release of Nrf2 from Keap1. Nrf2 is stabilized and translocate to the nucleus, where it heterodimerizes with MAF proteins, to bind to the antioxidant responsive element which leads to activation of cytoprotective genes.

Publication

Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis. (2012) César López-Camarillo, et al. Int J Mol Sci. 2012;13(1):142-172. Figure: F2. All organisms Drosophila melanogaster Homo sapiens

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