16 Matters of Life and Death: Translation Initiation during Apoptosis

Recent studies have identified several mechanistic links between the regulation of translation and the process of apoptosis induced via either receptor-dependent or receptor-independent mechanisms. Rates of protein synthesis are controlled by a wide range of agents that induce cell death, with many changes that occur to the translational machinery preceding overt apoptosis and loss of cell viability. In this chapter, we summarize the temporal regulation of translation initiation in response to the activation of apoptosis focusing on (1) early changes in protein phosphorylation, (2) specific proteolytic cleavage of initiation factors, (3) selective maintenance of populations of mRNA associated with the translational machinery, and (4) potential role for the reported increases in the cleavage of ribosomal RNA and increased turnover rates of mRNA. Any one event or combination of such events influences the translational capacity of the cell, allowing it to make a critical decision between survival and a commitment to die. Posttranscriptional control has a central role in this choice as the level of expression and activity of many effector proteins required for this decision are regulated at the translational level. APOPTOSIS Apoptosis as a phenomenon of programmed cell death by a suicide mechanism was first described by Kerr et al. (1972), with the morphological characteristics of apoptosis, which are distinct from those of a necrotic cell, being defined a year later (Schweichel and Merker 1973). The first noticeable physical change in a cell undergoing apoptosis is the condensation of the chromatin within the nucleus. The cytoplasm of the cell...