Caspase recruitment domain family member 8 (CARD8)

Caspase recruitment domain family member 8 (CARD8) is a cytosolic adaptor protein belonging to the death domain superfamily, characterized by the presence of a caspase recruitment domain (CARD) and a FIIND (function to find domain). CARD8 is a key regulator of apoptotic and inflammatory signaling, functioning as an inflammasome sensor, particularly responsive to pathogen and damage-associated signals in human cells. Upon activation, CARD8 undergoes auto-proteolytic cleavage, releasing its C-terminus, which self-oligomerizes to form the CARD8 inflammasome. This complex directly recruits and activates pro-caspase-1, resulting in the cleavage of gasdermin D, initiation of pyroptosis, and secretion of inflammatory cytokines. CARD8 also inhibits NF-kappa-B signaling, playing an anti-inflammatory role. Genetic variants of CARD8 have been associated with increased risk for chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. CARD8 expression is upregulated in certain cancers and is implicated in immune response modulation and cell death regulation.

Other names

CARD8TUCANCARDINALDACARKIAA0955NDPPNDPP1CARD8-CT (C-terminus)CARD8-NT (N-terminus)CARD inhibitor of NF-kappa-B-activating ligandstumor up-regulated CARD-containing antagonist of CASP9

Direct recruitment and activation of pro-caspase-1, leading to gasdermin-D cleavage and pyroptosis (cell lytic death); Negative regulation of NF-kappa-B, reducing inflammatory signaling