All along the watchtower: on the regulation of apoptosis regulators

Members of the expanding family of Bcl-2-like proteins have emerged as impo rtant regulators of programmed cell death, and recent studies have unearthe d numerous mechanisms for regulating the function of these death agonists a nd antagonists, In addition to the transcriptional control of gene expressi on, these mechanisms include post-translational events such as phosphorylat ion, proteolysis, and the induction of conformational changes, which may ei ther activate or inactivate these molecules, Interaction with homologous an d nonhomologous proteins and specific subcellular targeting of Bcl-2-like p roteins are other means of fine-tuning the cellular response to noxious sti muli. Recently, considerable attention has turned to the regulation of so-c alled BH3-only molecules, which appear to act as stress sensors that relay signals to other pro- or antiapoptotic family members, We discuss how the r egulation of these apoptosis regulators may control the ultimate fate of th e cell.-Fadeel, B., Zhivotovsky, B., Orrenius, S. All along the watchtower: on the regulation of apoptosis regulators.