Granzymes are a family of structurally related serine proteases that differ markedly in their substrate specificities. Although these proteases were predicted to function as intracellular and/or extracellular proteases in processes ranging from cell death to extracellular matrix cleavage to viral inactivation, intense research over the past two decades has focused primarily on their contributions as intracellular proteolytic mediators of cell death. This can be attributed at least in part to landmark studies by Hayes et al. demonstrating a synergistic cytotoxic effect when cells were exposed to perforin/cytolysin and granzymes. Since then, and perhaps fostered by the exponential growth of apoptosis research funding in the 1990s, there have been relatively fewer investigations into the potential broader functionality of these proteases with respect to non-apoptotic and/or perforin-independent functions.
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