FLICE-Inhibitory Proteins: Regulators of Death Receptor-Mediated Apoptosis

Abstract

Cell death is executed along several pathways. Apart from necrotic cell death occurring upon tissue injury, several distinct types of apoptosis have been observed. Apoptosis, or pro- grammed cell death, is critical for tissue homeostasis in mul- ticellular organisms. It plays an important role in many phys- iological processes, especially in development and in the immune system (39, 80). Many diseases are associated with either too much or too little apoptosis, such as AIDS, cancer, and autoimmunity (39). On the molecular level, the cell death program can be di- vided into three parts: initiation, execution, and termination of apoptosis. Apoptosis is initiated by a variety of stimuli, includ- ing growth factor withdrawal ("death by neglect"), UV or -ir- radiation, chemotherapeutic drugs, and death receptor signals. In most cases the execution phase is characterized by mem- brane inversion and exposure of phosphatidylserine, blebbing (zeiosis), fragmentation of the nucleus, chromatin condensa- tion, and DNA degradation. In the termination phase, "apo- ptotic bodies" are engulfed by phagocytes (39).