TNF signaling gets FLIPped off : TNF-induced regulation of FLIP

One of the major guardians of death receptor mediated programmed cell death is FLIP (Fas-associated protein with death domain-like IL-1ß-converting enzyme (FLICE) inhibitory protein). As an important modulator of apoptosis, FLIP regulates life and death in various types of normal cells and tissues, such as lymphoid cells, and renders resistance to death receptor-mediated apoptosis in many types of tumor cells. Therefore, understanding the signals that control FLIP is vital to understanding and controlling diseases such as cancer. Here, we discuss the mechanisms that regulate FLIP activation by tumor necrosis factor (TNF), and their functional significance in regulating apoptotic processes.