chapter  12
. Caspase-independent cell death
1. Introduction
ByMarcel Leist, Marja Jäättelä
Pages 8

Upon caspase inhibition, the alternative death pathways surface also in vivo. They are involved in processes such as the negative selection of lymphocytes (Smith et al, 1996; Doerfler et al, 2000), cavitation of embryoid bodies (Joza et al, 2001), embryonic removal of interdigital webs (Chautan et al, 1999), tumor necrosis fac­ tor (TNF)-mediated liver injury (Künstle et al, 1999), and the death of chondro­ cytes controlling the longitudinal growth of bones (Roach and Clarke, 2000). These examples may represent just the tip of the iceberg with regard to the complexity of death signaling in vivo. And the overlapping death pathways initiated by a single stimulus seem rather to be the rule than the exception (Holler et al, 2000; Charette et al, 2001; Joza et al, 2001). The examination of potential crossovers of death pathways that lead eventually to different phenotypic outcomes may offer a chance to understand which events do determine commitment to death, and which ones are instead involved in upstream signaling or downstream execution.