Cleaved Caspase-4 (Asp270)/Caspase-5 (Asp327) (F3Q2F) Rabbit Monoclonal Antibody #48139

Canonical activation of the inflammatory necrotic form of cell death, pyroptosis, occurs following inflammasome-mediated activation of caspase-1, leading to cleavage of gasdermin D (1,2). Alternatively, non-canonical cleavage of gasdermin D can be triggered by direct binding of bacterial lipopolysaccharide (LPS) to additional caspases, specifically mouse caspase-11 or human caspase-4 and caspase-5 (2-4). Unlike caspase-4, caspase-5 expression is strongly regulated by inflammatory signals such as LPS and interferon-γ (5). Caspase-4 and caspase-5 activation requires proteolytic processing between three domains: a cascade activation and recruitment domain (CARD), followed by the large and small subunits that form the active protease (6-10). LPS binding to the CARD domain results in cleavage of caspase-4 between the large and small subunits located at Asp270 and Asp289 and at Asp59 in the prodomain (11,12). Equivalent sites are found on caspase-5 at Asp327, Asp346, and Asp137 (13).