Caspase-1

By Victoria Osinski, PhD

By Victoria Osinski

By Stephanie Melchor

The inflammasome is a multi protein complex that is an important component of the innate immune response. The inflammasome is able to sense and respond to pathogen infections by recognizing pathogen-associated molecular patterns and mediating the secretion of inflammatory cytokines. Of the various types of inflammasomes, NLRP3/NALP3 is unique because of the diverse range of microbes it is able to detect (1).

Apoptosis, also called programmed cell death, is an essential process in development and disease. The signaling networks that carry out apoptosis is consists of a series of endoproteases called caspases which are synthesized as inactive zymogens. Caspses are grouped into two classes: initiator caspases and effector caspases. Initiator caspases are activated by the assembly of multi-protein complexes such as the death-inducing signaling complex (DISC) (1).

Caspase-7 is an effector caspase with important roles in mediating cell death signaling. As an effector caspase, caspase-7 is cleaved and activated by initiator caspases such as caspase-1 (1). Like other caspase family proteins, caspase-7 contains a catalytic cysteine residue in its active site. This allows caspase-7 to cleave various substrates, such as PARP, to aid in the degradation and destruction of the cell (2).

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).

Caspases are a family of cysteine-aspartic acid proteases that cleave caspase proenzymes as well as other protein substrates. Caspases are well known for their role in apoptosis, but they also play a significant role in other cellular processes including inflammation (1). Apoptotic caspases include Caspases-3, -6, -7, -8, and -9. Meanwhile, human inflammatory caspases include Caspases-1, -4, -5, and -12.