Journal
CELL DEATH AND DIFFERENTIATION
Volume 15, Issue 10, Pages 1533-1541Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2008.41
Keywords
apoptosis; caspase-8; lymphotoxin; signaling; TNF
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Funding
- Ares Trading SA, Switzerland, a Center of Excellence Grant from the Flight Attendant Medical Research Institute (FAMRI)
- Kekst Family Center for Medical Genetics at the Weizmann Institute of Science
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Early in the exploration of the chemical nature of life, it was widely believed that the molecules of living organisms, by their very nature, differ from those of inorganic material molecules and possess a vital force ('elan vital'). Similarly, early scientific thinking on the subject of cell death and its induction by cytotoxic cells of the immune system was pervaded by a sense that the molecules mediating these functions possess intrinsic deadly activity and are dedicated exclusively to death-related tasks. This impression was also reflected in the initial notions of the mode of action of intracellular proteins that signal for death. It is now gradually becoming clear, however, that proteins participating in death induction also have functions unrelated to death. Nevertheless, as exemplified by studies of the function of caspase-8 (an enzyme that signals both for activation of the extrinsic cell-death pathway and for non-death-related effects), analysis of the mechanistic basis for such heterogeneity might allow identification of distinct structural determinants in the proteins participating in death induction that do bear death specificity.
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