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Proteases in Apoptosis: Pathways, Protocols and Translational Advances pp 31–51Cite as

Caspases – Key Players in Apoptosis

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Abstract

Caspases are the terminal proteases involved in apoptosis, as well as being involved in inflammation. The apoptotic caspases can be classified as either initiator or effector caspases based on both their position in the caspase cascade and their activation mechanism. Initiator caspases require dimerization to be activated, and cleavage of a loop called the intersubunit linker stabilizes the active enzyme. Effector caspases, on the other hand, are found as dimers in the cell and cleavage of the intersubunit linker is the key step in their activation.

The name caspase is short for cysteinyl aspartate-specific protease. As their name suggests, these enzymes hydrolyze peptide bonds after certain aspartate residues using a catalytic cysteine (with the aid of an active-site histidine residue). Caspases can be inhibited by endogenous inhibitors such as XIAP, by synthetic inhibitors which target either the active site or an allosteric site, or by post-translational modification. Further research is needed to find novel activators and inhibitors of caspases to treat diseases which involve misregulation of apoptosis.

Funding: This work was supported by a grant from the NIH (National Institutes of Health) [grant number GM065970 (to A.C.C.)].

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Abbreviations

ASC:

Apoptosis-associated speck-like protein containing a CARD

CARD:

Caspase activation and recruitment domain

Caspase:

Cysteinal aspartate-specific protease

DAMPs:

Danger-associated molecular patterns

DD:

Death domain

DISC:

Death inducing signaling complex

FADD:

Fas-associated death domain

FasL:

Fas ligand

FLICE:

FADD-like interleukin 1β-converting enzyme

FLIP:

FLICE-like inhibitory protein

FLIPL :

Long splice variant of FLIP which forms a heterodimer with caspase-8

FLIPS :

Short splice variant of FLIP which blocks caspase-8 from binding death receptor

ICE:

Interleukin 1β-converting enzyme

IL-1β:

Interleukin 1β

IL-18:

Interleukin 18

PS:

Phosphatidylserine

Smac:

Second mitochondrial activator of caspases

TNFR:

Tumor necrosis factor receptor

XIAP:

X-linked inhibitor of apoptosis protein

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Author notes

  1. A. Clay Clark (Professor and Chair)

    Present address: Department of Biology, University of Texas at Arlington, Arlington, TX, 76019, USA

Authors and Affiliations

  1. Department of Molecular and Structural Biochemistry, North Carolina State University, 128 Polk Hall, Raleigh, NC, 27695-7622, USA

    Christine E. Cade

  2. Department of Molecular and Structural Biochemistry and Center for Comparative Medicine and Translational Research, North Carolina State University, 128 Polk Hall, Raleigh, NC, 27695-7622, USA

    A. Clay Clark (Professor and Chair)

Authors
  1. Christine E. Cade
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  2. A. Clay Clark
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Correspondence to A. Clay Clark .

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Editors and Affiliations

  1. Tata Memorial Centre, Integrated Biophysics and Structural Biology Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Navi Mumbai, India

    Kakoli Bose

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Cade, C.E., Clark, A.C. (2015). Caspases – Key Players in Apoptosis. In: Bose, K. (eds) Proteases in Apoptosis: Pathways, Protocols and Translational Advances. Springer, Cham. https://doi.org/10.1007/978-3-319-19497-4_2

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