Cellular FLICE-like inhibitory proteins (c-FLIPs): Fine-tuners of life and death decisions

c-FLIP proteins (isoforms: c-FLIPL, c-FLIPS, and c-FLIPR) play an essential role in the regulation of death receptor (DR)-induced apoptosis and NF-κB activation. Here, we discuss multiple mechanisms by which c-FLIPs control NF-κB activation and the life/death decision made in cancer and immune cells. We focus on the role of c-FLIP in cellular signaling. We concentrate on c-FLIP protein modifications as well as on the regulation of c-FLIP expression levels. Furthermore, we discuss in detail how the exact quantity and dynamics of different c-FLIP isoforms in the cell influence the induction of pro- versus anti-apoptotic pathways.