| 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. | |
| | |
MedLine Citation:
|
PMID: 20704564 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cytotoxic lymphocytes eliminate infected cells and tumours via the perforin-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 remained 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. |
| | |
Authors:
|
Gina B Scott; Paul A Bowles; Erica B Wilson; Josephine L Meade; Boon Chuan Low; Adam Davison; G Eric Blair; Graham P Cook |
Related Documents
:
|
12882504 - Hydrogen peroxide-induced cell death in a human retinal pigment epithelial cell line, a... 17194804 - Simultaneous induction of apoptotic and survival signaling pathways in macrophage-like ... 20101204 - Cross talk between apoptosis and autophagy by caspase-mediated cleavage of beclin 1. 12133234 - Tributyltin induces human neutrophil apoptosis and selective degradation of cytoskeleta... 19283744 - Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb... 9556354 - Melatonin, immune modulation and aging. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Biochemical journal Volume: 431 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-10-12 Completed Date: 2010-10-27 Revised Date: 2011-09-06 |
Medline Journal Info:
|
Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
|
Languages: eng Pagination: 423-31 Citation Subset: IM |
Affiliation:
|
Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Carrier Proteins / chemistry, immunology, metabolism* Caspases / metabolism Cell Line Conserved Sequence Cytotoxicity, Immunologic* Granzymes / immunology, metabolism* Humans Killer Cells, Natural / immunology*, metabolism Molecular Sequence Data Sequence Alignment Substrate Specificity |
| Chemical | |
Reg. No./Substance:
|
0/BNIP2 protein, human; 0/Carrier Proteins; EC 3.4.21.-/Granzymes; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6...
Next Document: Key motifs in EBV (Epstein-Barr virus)-encoded protein kinase for phosphorylation activity and nucle...