CASP1 gene

The CASP1 gene (CASP1 stands for: Caspase 1) is a protein-coding gene located on chromosome 11q22.3. The CASP1 gene encodes a protein that belongs to the family of cysteine-aspartic acid proteases (caspases). Alternative splicing leads to transcript variants that code for different isoforms.

The encoded protease, a thiol protease, 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 gasdermin-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: once activated by the formation of an inflammasome complex, it triggers a pro-inflammatory response by cleaving the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines involved in a variety of inflammatory processes (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 GSDMD

Caspases exist as inactive proenzymes that are proteolytically processed on conserved aspartic acid residues to form two subunits, one large and one small, which dimerize to form the active enzyme. The CASP1 protein was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in processes such as inflammation, septic shock and wound healing.

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.