Caspase-1

Caspase-1 is a protease, a thiol protease encoded by the CASP1 gene located on chromosome 11q22.3. Caspase-1 is a protein that belongs to the family of cysteine-aspartic acid proteases(caspases). It is involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin-18 (IL18) as well as the pyroptosis inducer gas dermin-D (GSDMD), into active mature peptides (Thornberry NA et al. 1992; Shi J et al. 2015; Ball DP et al. 2020). The enzyme plays a key role in cell immunity as a trigger of an inflammatory response:

In resting cells, caspase-1 is present as a catalytically inactive proenzyme. However, the formation of the inflammasome complex initiates the autocatalytic activation of the enzyme. The activated caspase-1, originally known as IL-1-converting enzyme (ICE), now catalyzes the conversion of pro-IL-1beta into its active form IL-1beta, but also the cleavage of other cytokines of the same family, such as pro-IL-18 and pro-IL-33, is catalyzed by caspase-1 (Ball DP et al. 2020). Furthermore, the sequential activation of caspases plays a central role in the execution phase of cell apoptosis. Also triggers pyroptosis, a programmed lytic cell death, by cleavage of gas dermin-D.

1. Ball DP et al. (2020) Caspase-1 interdomain linker cleavage is required for pyroptosis. Life Sci Alliance 3:e202000664.
2. Shi J et al. (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526:660-665.
3. Thornberry NA et al. (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768-774.