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Caspase-3-mediated proteolysis is crucial to the apoptotic process, and studies have shown a central role for mitochondrial proteins in caspase-3 activation. It is demonstrated that the caspase-3 proenzyme has mitochondrial and cytosolic distribution in nonapoptotic cells. It is proposed that the caspase-3 precursor molecule mitochondrial subpopulation is linked to a distinct subset of Bcl-2 sensitive apoptotic signaling pathways.

An assay system that involves a MHC class II-matched or autologous allogeneic Epstein-Barr virus (EBV)-transformed B-cell line helps generate antigens from tumor cell lysates to analyze whether melanoma-specific CD4+ T cells identify shared melanoma antigens. The assay system reveals that the CD4+ T cells recognize the melanoma-associated antigens from the tyrosinase gene that also expresses the CD8+ T cells-identified class I restricted epitopes. The T cell clones exhibit a single, distinct recognition scheme, indicating the existence of an immunodominant epitope that is a tyrosinase gene product.

Caspases are an extended family of cysteine proteases that play critical roles in apoptosis. Animals deficient in caspases-2 or -3, which share very similar tetrapeptide cleavage specificities, exhibit very different phenotypes, suggesting that the unique features of individual caspases may account for distinct regulation and specialized functions. Recent studies demonstrate that unique apoptotic stimuli are transduced by distinct proteolytic pathways, with multiple components of the proteolytic machinery clustering at distinct subcellular sites. We demonstrate here that, in addition to its nuclear distribution, caspase-2 is localized to the Golgi complex, where it cleaves golgin-160 at a unique site not susceptible to cleavage by other caspases with very similar tetrapeptide specificities. Early cleavage at this site precedes cleavage at distal sites by other caspases. Prevention of cleavage at the unique caspase-2 site delays disintegration of the Golgi complex after delivery of a pro-apoptotic signal. We propose that the Golgi complex, like mitochondria, senses and integrates unique local conditions, and transduces pro-apoptotic signals through local caspases, which regulate local effectors. Key words: signaling * subcellular * substrate * coiled coil * protease