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A lysosomal protease enters the death scene
Guy S. Salvesen
Guy S. Salvesen
Published January 1, 2001
Citation Information: J Clin Invest. 2001;107(1):21-23. https://doi.org/10.1172/JCI11829.
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Commentary

A lysosomal protease enters the death scene

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Abstract

Authors

Guy S. Salvesen

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Figure 1

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Two initiation pathways, triggered by separate events, converge to execu...
Two initiation pathways, triggered by separate events, converge to execute apoptosis. The extrinsic pathway (lighter shading) encompasses the extracellular ligation of death receptors by their cognate ligands, resulting in receptor clustering, adapter recruitment, and activation of the apical protease caspase 8. Thus, death receptors act as a conduit for the transmission of extracellular death signals into the cell’s interior. The intrinsic pathway (darker shading) responds primarily to cellular stress (ionizing radiation, cytotoxic drugs, etc.), with the mitochondrion acting as an important integrator. Pro- and antiapoptotic members of the Bcl-2 family (Bax and Bcl-2 serve as examples) regulate the lethal stress-response threshold. Activation of the apical protease caspase 9 occurs when it is driven into an active conformation by its cofactor Apaf-1, which itself requires prior binding to cytochrome c. Both pathways activate the executioner proteases caspases 3 and 7. The proapoptotic Bcl-2 family member Bid is at an intersection between the two initiation pathways. An important feature of the extrinsic pathway is that several receptors, in response to their cognate ligands, converge their death signals by activating caspase 8. Now, new evidence (11) proposes a role for the lysosomal protease cathepsin B in the extrinsic pathway triggered by TNF-α.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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