Bcl-2 blocks perforin-induced nuclear translocation of granzymes concomitant with protection against the nuclear events of apoptosis

Abstract

Cytolytic granule-mediated target cell killing is effected in part through the synergistic action of the membrane-acting protein perforin and serine proteases such as granzymes (Gr) A and B. In this study, we examine the subcellular distribution of granzymes in the presence of perforin and the induction of apoptosis in mouse FDC-P1 myeloid and YAC-1 lymphoma cells that express the proto-oncogene bcl2. Using confocal laser scanning microscopy to visualize and quantitate subcellular transport of fluoresceinated granzyme, we find that granzyme entry into the cytoplasm in the absence of perforin is not impaired in the bcl2-expressing lines. However, perforin-dependent enhancement of granzyme cel..