Role of cFLIP/CFLAR protein in the activation and regulation of cell death

Programmed cell death as a natural mechanism plays essential role in development and homeostasis maintenance through removal of damaged, unwanted or dangerous cells. The cell death is an irreversible proces must be strictly regulated and thus defects in the regulation of cell death could lead to serious/fatal diseases. There are also one of the reasons why cell death regulating mechanisms are subjects of intense research nowadays. c-FLIP is one of several important cell death regulators. Three distinct isoforms of c-FLIP were detected on the protein level in human organism (long c-FLIPL and two shorter variants c-FLIPS and c-FLIPR) that interact their main cellular partner procaspase 8. The functional consequences of their interaction (enhancement or suppression of procaspase 8 selfprocessing) depend on the cellular level of c-FLIP, expressed splice variants and extracellular signaling. As c-FLIP is an important component of cell death signaling pathways (apoptosis and regulated necrosis), its expression and functional posttranslational modifications are strictly regulated by several mechanisms. Upregulation of c-FLIP levels has been found in various types of tumor cells that are often resistant to anticancer treatment