ABSTRACT
Apoptosis is a genetically controlled cell death pathway that is triggered by diverse stimuli (reviewed in [1]). Although the phenomenon of apoptosis has been known for a long time, awareness of its critical role in metazoan biology has been slow to evolve, principally because cell death is commonly viewed as a pathological phenomenon restricted to tissue subject to damage or trauma. Recently, however, it has become increasingly clear that apoptosis is a fundamental component of tissue homeostasis. The hunt for genes that control apoptosis is at present an intense area of research, mainly because genetic lesions that restrict cell death also grossly affect cell population number, thereby leading to a number of diverse pathologies. For example, transgenic mice in which over-expression of the apoptosis-suppressing protooncogene bcl-2 is targeted to the B cell lineage exhibit a substantially expanded B-cell population. Although this hyperplasia is not at first clinically pathological, from these hyperplastic cells secondary tumourigenic lesions arise with high frequency. Although there is as yet no overall defined molecular pathway for apoptosis, several gene products have been shown to either induce (c-Myc, p53, Bax, Fas) or suppress (Bcl-2, Abl, p19EIB) it. In this chapter, these key genetic players and their effects on cell death will be reviewed, with particular attention paid to the possible interactions that may occur between these genes that lead to malignancy.
