Identification of the BCL2/adenovirus E1B-19K protein-interacting protein 2 (BNIP-2) as a granzyme B target during human natural killer cell-mediated killing

[摘要]：Cytotoxic lymphocytes eliminate infected cells and tumours via the perform-mediated delivery of pro-apoptotic serine proteases known as granzymes Granzyme B triggers apoptosis via the cleavage of a repertoire of cellular proteins leading to caspase activation and mitochondrial depolarization A simple bioinformatics strategy identified a candidate granzyme B cleavage site in the widely expressed BNIP-2 (BCL2/adenovirus E1B-19K protein-interacting protein 2) Granzyme B cleaved recombinant BNIP-2 in vitro and endogenous BNIP-2 was cleaved during the NK (natural killer) cell-mediated killing of tumour cells Cleavage required the site identified in the bioinformatics screen and was caspase-independent Expression of either full-length BNIP-2 or a truncated molecule mimicking the granzyme B cleaved form was pro-apoptotic and led to the caspase-dependent cleavage of BNIP-2 at a site distinct from granzyme B cleavage Inhibition of BNIP-2 expression did not affect the susceptibility to NK cell-mediated killing Furthermore, target cells in which BID (BH3-interacting domain death agonist) expression was inhibited also renamed highly susceptible to NK cell-mediated killing revealing redundancy in the pro-apoptotic response to human cytotoxic lymphocytes Such redundancy reduces the opportunity for escape from apoptosis induction and maximizes the chances of immune-mediated clearance of infected cells or tumour cells

[全文传递流程]：

一般上传文献全文的时限在1个工作日内