Recombinant Human CARD8 protein

Specifications

Form

Liquid

General info

Function

Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis of CD4(+) T-cells and macrophages (PubMed : 11408476, PubMed : 11821383, PubMed : 15030775, PubMed : 32051255, PubMed : 32840892, PubMed : 33542150, PubMed : 34019797, PubMed : 36357533). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed : 11408476, PubMed : 11821383, PubMed : 15030775, PubMed : 36357533). Acts as a recognition receptor (PRR) : recognizes specific pathogens and other damage-associated signals, such as HIV-1 protease activity or Val-boroPro inhibitor, and mediates CARD8 inflammasome activation (PubMed : 32840892, PubMed : 33542150, PubMed : 36357533). In response to pathogen-associated signals, the N-terminal part of CARD8 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes to initiate the formation of the inflammasome complex : the CARD8 inflammasome directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (PubMed : 32051255, PubMed : 32840892, PubMed : 33053349, PubMed : 33542150, PubMed : 36357533). Ability to sense HIV-1 protease activity leads to the clearance of latent HIV-1 in patient CD4(+) T-cells after viral reactivation; in contrast, HIV-1 can evade CARD8-sensing when its protease remains inactive in infected cells prior to viral budding (PubMed : 33542150). Also acts as a negative regulator of the NLRP3 inflammasome (PubMed : 24517500). May also act as an inhibitor of NF-kappa-B activation (PubMed : 11551959, PubMed : 12067710).. Caspase recruitment domain-containing protein 8. Constitutes the precursor of the CARD8 inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals.. Caspase recruitment domain-containing protein 8, N-terminus. Regulatory part that prevents formation of the CARD8 inflammasome : in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus), preventing activation of the CARD8 inflammasome (PubMed : 33542150). In response to pathogen-associated signals, this part is ubiquitinated by the N-end rule pathway and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the CARD8 inflammasome (Probable) (PubMed : 32558991).. Caspase recruitment domain-containing protein 8, C-terminus. Constitutes the active part of the CARD8 inflammasome (PubMed : 32840892, PubMed : 34019797). In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of CARD8 (Caspase recruitment domain-containing protein 8, N-terminus), preventing activation of the CARD8 inflammasome (PubMed : 33542150). In response to pathogen-associated signals, the N-terminal part of CARD8 is degraded by the proteasome, releasing this form, which polymerizes to form the CARD8 inflammasome complex : the CARD8 inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis (PubMed : 32840892, PubMed : 33542150).

Post-translational modifications

Caspase recruitment domain-containing protein 8. Undergoes autocatalytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals.. Caspase recruitment domain-containing protein 8, N-terminus. Ubiquitinated by the N-end rule pathway in response to pathogens and other damage-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes and forms the CARD8 inflammasome.. (Microbial infection) Proteolytic cleavage by HIV-1 protease in the disordered region and within the ZU5 region of the FIIND domain promotes ubiquitination of the N-terminal part by the N-end rule pathway and degradation by the proteasome, releasing the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes and forms the CARD8 inflammasome.. Isoform 1. Undergoes less autocatalytic processing within the FIIND domain compared to isoform 5.

Subcellular localisation

Nucleus