Caspases – Key Players in Apoptosis

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.

Caspase‐3: Structure, function, and biotechnological aspects

“…Among all these therapeutic enzymes, caspase‐3 is one of the most substantial ones. Caspase‐3 is a protein (also called CPP32 or apopain), encoded by the CASP3 gene; it is a member of the endoproteases (cysteine‐aspartic proteases) family, which uses a cysteine, as the catalytic nucleophile, at its active site in order to cleave the target protein on its aspartic acid residue 1 . Caspase‐3 is initially synthesized as an immature zymogen (procaspase), requiring specific proteolysis to become activated.…”

CRISPR Technologies in Chinese Hamster Ovary Cell Line Engineering

“…Apoptosis is a popular target to improve culture longevity and productivity as it is the major cause of death of CHO production lines [84]. Caspases are well-known executioners of apoptosis [85] and therefore an obvious target of choice for KO. Knowledge generated in other mammalian cells together with the report about siRNA-mediated co-downregulation of caspase-3 and caspase-7 in CHO cells, which led to increased cell viability and extension of culture longevity [86], motivated researchers to study the impact of caspase KO on CHO cell line performance.…”

Validation of the Intermolecular Disulfide Bond in Caspase-2

“…It is now appreciated that caspases are involved in many heterogenous contexts, including the immune response to intracellular infection [4][5][6]. Broadly, caspases are divided based on their function in apoptosis as initiators and executioners, or in facilitating pyroptosis [7]. Diverse signals will activate specific caspases, which then cleave specific protein substrates.…”