Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide -induced pyroptosis . Also indirectly activates the NLRP3 and NLRP6 inflammasomes . Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS and GSDMD . In contrast to its human ortholog, does not cleave IL18 . Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B and IL18 . In the non-canonical inflammasome, CASP4/CASP11 is activated by direct binding to the lipid A moiety of LPS without the need of an upstream sensor . LPS-binding promotes CASP4/CASP11 activation and CASP4/CASP11-mediated cleavage of GSDMD, followed by pyroptosis of infected cells and their extrusion into the gut lumen . Also indirectly promotes secretion of mature cytokines downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes . Involved in NLRP3-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin . Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid , a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B and IL18 secretion . Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity . The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria . Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection . Activation of the non-canonical inflammasome in brain endothelial cells can lead to excessive pyroptosis, leading to blood-brain barrier breakdown . Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation . May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid . Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4/CASP11 that recognizes and binds the Gasdermin-D, C-terminal part . In contrast, it does not directly process IL1B . During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation .

Caspase-4 (CASP-4) (EC 3.4.22.64) (Caspase-11) (CASP-11) (Protease ICH-3) [Cleaved into: Caspase-4 subunit p10; Caspase-4 subunit p20]

p70343

Mouse

WB

WB 1:1000

~43 kD

Rabbit

50mM Tris-Glycine(pH 7.4), 0.15M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

Store at -20°C. Stable for 12 months from date of receipt.