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 1

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Caspase structure. (A) The caspase family. Three major groups of caspase...
Caspase structure. (A) The caspase family. Three major groups of caspases are presented. Group I: inflammatory caspases; group II: apoptosis initiator caspases; group III: apoptosis effector caspases. The CARD, the DED, and the large (p20) and small (p10) catalytic subunits are indicated. (B) Scheme of procaspase activation. Cleavage of the procaspase at the specific Asp-X bonds leads to the formation of the mature caspase, which comprises the heterotetramer p202–p102, and the release of the prodomain. The residues involved in the formation of the active center are shown. (C) The 3D structure of caspase-3 heterotetramer. Each heterodimer is formed by hydrophobic interactions resulting in the formation of mostly parallel β-sheets, composed of 6 antiparallel β-strands. Two heterodimers fit together with formation of a 12-stranded β-sheet that is sandwiched by α-helices. N and C termini of the small and large protease subunits are indicated.