Signalling by proteolysis: death receptors induce apoptosis |
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Authors: | M Muzio |
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Institution: | (1) Department of Immunology and Cell Biology, Mario Negri Institute, Via Eritrea 62, I-20157 Milan, Italy |
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Abstract: | Apoptosis, or programmed cell death, is a genetically regulated mechanism with a central role in both metazoan development
and homeostasis. Death receptors (Fas, TNFR-2, DR3, and TRAIL receptors) induce apoptosis upon ligation to cognate ligands
or ectopic expression. The assembly of a death-inducing signalling complex occurs in a hierarchical manner upon receptor activation.
The death domain of the receptor binds to the corresponding domain of the adapter molecule FADD, which in turn recruits the
zymogen form of the death protease FLICE (MACH/caspase-8). Upon approximation, FLICE “zymogens” attain a sufficient concentration
to self-activate and to trigger the apoptotic pathway. For the first time, a transmembrane receptor directly engaging a protease
at the signalling complex and subsequently triggering a proteolytic signalling cascade is described. |
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Keywords: | Apoptosis Caspase Signalling Tumor necrosis factor Apo |
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