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37.3: Caspases

JoVE Core
Cell Biology

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37.3: Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.

Caspase Activation

Caspases are produced as inactive zymogens, called procaspases. The procaspases contain four loops, L1 to L4. During activation, L2 is cleaved, and the monomeric subunits dimerize. The initiator procaspases also have long pro-domains such as the death effector domain (DED) or caspase recruitment domain (CARD). These pro-domains interact with the adaptor molecules to cleave and activate the initiator caspases. Conversely, executioner caspases have short pro-domains and are cleaved by the active initiator caspases.

Caspases and Homeostasis

Cell proliferation and cell death are both essential to maintain homeostasis in multicellular organisms. The over- and under-activation of caspases, thus, can lead to many diseases. For example, decreased caspase activity is a common feature of cancerous cells. Many infectious diseases also decrease caspase activity. For example, the p35 protein released by certain viruses binds the caspases, thus preventing caspase activation and blocking apoptosis. In contrast, the over-activation of inflammatory caspases causes sepsis due to increased inflammatory response. Excessive activation of caspases can also cause diseases such as Alzheimer's, Parkinson’s, and Huntington's.


Caspases Cysteine Proteases Apoptosis Ced3 Gene C.elegans Interleukin-1-beta Converting Enzyme ICE Inflammatory Response Pro-inflammatory Cytokines Immune Cells Pathogens Procaspases L1 To L4 Loops Dimerize Pro-domains Death Effector Domain Caspase Recruitment Domain Adaptor Molecules Initiator Caspases Executioner Caspases Homeostasis Cell Proliferation Cell Death Over-activation Under-activation Diseases

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