c-Rel in Epidermal Homeostasis: A Spotlight on c-Rel in Cell Cycle Regulation

To maintain proper skin barrier function, epidermal homeostasis requires a subtly governed balance of proliferating and differentiating keratinocytes. While differentiation takes place in the suprabasal layers, proliferation, including mitosis, is usually restricted to the basal layer. Only recently identified as an important regulator of epidermal homeostasis, c-Rel, an NF-κB transcription factor subunit, affects the viability and proliferation of epidermal keratinocytes. In human keratinocytes, decreased expression of c-Rel causes a plethora of dysregulated cellular functions including impaired cell viability, increased apoptosis, and abnormalities during mitosis and cell cycle regulation. On the other hand, c-Rel shows aberrant expression in many epidermal tumors. Here, in the context of its role in different cell types and compared with other NF-κB subunits, we discuss the putative function of c-Rel as a regulator of epidermal homeostasis and mitotic progression. In addition, implications for disease pathophysiology with perturbed c-Rel function and abnormal homeostasis, such as epidermal carcinogenesis, will be discussed.