Starting and propagating apoptotic signals in UVB irradiated keratinocytes

The ultraviolet (UV) B portion of the UV light has been recognized as the most prominent risk factor for the development of skin cancer, the most common malignancy in the Caucasian population. At the cellular level, UVB signal transduction regulates replicative arrest and DNA repair, gene expression and, when damage is beyond repair, apoptotic cell death, which is induced to protect the host against the accumulation of potentially mutagenic keratinocytes. An increasing body of evidence indicates that the UVB response in skin is a complex and multifaceted biological process. The UVB signal transduction originates at multiple intracellular sites, and the cross talk between dedicated molecular mediators acting within a complex signal network, determines whether the UVB damaged cell will survive, proliferate or die. However, very little is known about the original targets or direct chromophores that put in motion the UVB response in its main target: the keratinocyte. In this review we discuss the recent identification of signalling pathways linking apical UVB mediated damaging events with the induction of apoptosis. Understanding the molecular mechanisms that underlie the process of apoptotic cell death in UVB exposed keratinocytes, is of outmost importance to reveal how defects in apoptotic pathways can contribute to skin cancer.