Caspases: pharmacological manipulation of cell death
Inna N. Lavrik, … , Alexander Golks, Peter H. Krammer
Inna N. Lavrik, … , Alexander Golks, Peter H. Krammer
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2665-2672. https://doi.org/10.1172/JCI26252.
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Review Series

Caspases: pharmacological manipulation of cell death

Abstract

Caspases, a family of cysteine proteases, play a central role in apoptosis. During the last decade, major progress has been made to further understand caspase structure and function, providing a unique basis for drug design. This Review gives an overview of caspases and their classification, structure, and substrate specificity. We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death.

Authors

Inna N. Lavrik, Alexander Golks, Peter H. Krammer

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Figure 2

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Scheme of procaspase-8 processing at the CD95 DISC. CD95 DISC formation ...
Scheme of procaspase-8 processing at the CD95 DISC. CD95 DISC formation is triggered by extracellular cross-linking with CD95L (depicted in red), which is followed by oligomerization of the receptor. FADD/MORT1 is recruited to the DISC by DD interactions (shown in red); procaspase-8 and -10 as well as c-FLIP proteins are recruited to the DISC by homophilic DED interactions (yellow). Upon recruitment to the DISC, procaspase-8 undergoes processing by forming dimers (depicted in green). (A) The first step of procaspase-8 cleavage occurs between 2 protease subunits. The site of cleavage is shown by a black arrow. As a result of the first cleavage step the p10 subunit is formed, which is not released into the cytosol but remains bound to the DISC as it is involved in the interactions with the large protease subunits. (B) The second cleavage step takes place between the prodomain and the large protease subunit at Asp216. As a result of this cleavage step the active caspase-8 heterotetramer is formed, which is then released into the cytosol. (C) Prodomain p26/p24 remains bound to the DISC.