Ignition of p53 Bomb Sensitizes Tumor Cells to Granzyme K-Mediated Cytolysis

摘要: Inactivation of tumor suppressor p53 results in loss the apoptosis-regulating function protein cells. Restoration wild-type expression mutant cells increases susceptibility to CTL-mediated cytolysis. However, direct role regulating sensitivity NK cell-mediated lysis and functional relationship between granzymes control killing are still poorly documented. In this study, we found that can sensitize tumor-killing granzyme K-mediated Granzyme K is constitutively expressed high levels induces rapid caspase-independent cell death. may exert a critical clearance. associates with physiological substrate K. was processed three cleavage products p40, p35, p13 fragments at Lys 24 305 . These harbor strong proapoptotic activities amplify action potentiate sensitivity. Therefore, as cytotoxic bomb be triggered by K, leading potentiating efficacy.