inflammasome

By Stephanie Melchor

Caspases are endoproteases that play important roles in the regulation of cell death and apoptosis. Caspase active sites contain a catalytic cysteine residue essential for the proteolytic cleavage of their substrates at conserved aspartic acid residues (1). Caspases are produced as inactive procaspase monomers in order to regulate their activity. Upon dimerization procaspases are cleaved to produce their active form (1). Caspases are typically grouped by their role in either cell death or inflammation.

Caspase-1 is an enzyme involved in the conversion of interleukin-1 into its active secreted form. Interleukin-1 mediates inflammatory responses during infection and disease. Caspase-1 is recruited to and activated by the inflammasome complex (1). Under normal cellular conditions caspase-1 exists in an inactive pro form. Following stimulation with LPS or various microbial signals procaspase-1 is proteolytically cleaved into 10- and 20-kDa subunits that are enzymatically active (2).

Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands. This regulated process then transmits downstream signals through adaptor molecules ending with the caspase cysteine proteases. Caspase 11 has a heterotetrameric structure consisting of two anti-parallel heterodimers. Upon activation, it is cleaved by an autocatalytic mechanism to give rise to individual subunits. This post-translational regulation enables rapid activation. Expression levels of caspase 11 are highest in lung and spleen.