Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis

Caspases are an extended family of cysteine proteases that play critical ro les in apoptosis. Animals deficient in caspases-2 or -3, which share very s imilar tetrapeptide cleavage specificities, exhibit very different phenotyp es, suggesting that the unique features of individual caspases may account for distinct regulation and specialized functions. Recent studies demonstra te that unique apoptotic stimuli are transduced by distinct proteolytic pat hways, with multiple components of the proteolytic machinery clustering at distinct subcellular sites. We demonstrate here that, in addition to its nu clear distribution, caspase-2 is localized to the Golgi complex, where it c leaves golgin-160 at a unique site not susceptible to cleavage by other cas pases with very similar tetrapeptide specificities. Early cleavage at this site precedes cleavage at distal sites by other caspases. Prevention of cle avage at the unique caspase-2 site delays disintegration of the Golgi compl ex after delivery of a pro-apoptotic signal. We propose that the Golgi comp lex, like mitochondria, senses and integrates unique local conditions, and transduces pro-apoptotic signals through local caspases, which regulate loc al effectors.