Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/121738
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival |
Author: | Viant, C. Guia, S. Hennessy, R.J. Rautela, J. Pham, K. Bernat, C. Goh, W. Jiao, Y. Delconte, R. Roger, M. Simon, V. Souza-Fonseca-Guimaraes, F. Grabow, S. Belz, G.T. Kile, B.T. Strasser, A. Gray, D. Hodgkin, P.D. Beutler, B. Vivier, E. et al. |
Citation: | Journal of Experimental Medicine, 2017; 214(2):491-510 |
Publisher: | Rockefeller University Press |
Issue Date: | 2017 |
ISSN: | 0022-1007 1540-9538 |
Statement of Responsibility: | Charlotte Viant, Sophie Guia, Robert J. Hennessy, Jai Rautela, Kim Pham ... Benjamin T. Kile ... et al. |
Abstract: | Natural killer (NK) cells are innate lymphoid cells with antitumor functions. Using an N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a strain with an NK cell deficiency caused by a hypomorphic mutation in the Bcl2 (B cell lymphoma 2) gene. Analysis of these mice and the conditional deletion of Bcl2 in NK cells revealed a nonredundant intrinsic requirement for BCL2 in NK cell survival. In these mice, NK cells in cycle were protected against apoptosis, and NK cell counts were restored in inflammatory conditions, suggesting a redundant role for BCL2 in proliferating NK cells. Consistent with this, cycling NK cells expressed higher MCL1 (myeloid cell leukemia 1) levels in both control and BCL2-null mice. Finally, we showed that deletion of BIM restored survival in BCL2-deficient but not MCL1-deficient NK cells. Overall, these data demonstrate an essential role for the binding of BCL2 to BIM in the survival of noncycling NK cells. They also favor a model in which MCL1 is the dominant survival protein in proliferating NK cells. |
Keywords: | Killer Cells, Natural |
Rights: | © 2017 Viant et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http ://www .rupress .org /terms /). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 4.0 International license, as described at https ://creativecommons .org /licenses /by -nc -sa /4 .0 /). |
DOI: | 10.1084/jem.20160869 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1049407 http://purl.org/au-research/grants/nhmrc/1066770 http://purl.org/au-research/grants/nhmrc/1057852 http://purl.org/au-research/grants/nhmrc/1027472 http://purl.org/au-research/grants/nhmrc/1047903 http://purl.org/au-research/grants/nhmrc/1078763 http://purl.org/au-research/grants/nhmrc/1016701 http://purl.org/au-research/grants/nhmrc/1057831 http://purl.org/au-research/grants/nhmrc/1054925 http://purl.org/au-research/grants/nhmrc/0461276 http://purl.org/au-research/grants/nhmrc/1020363 http://purl.org/au-research/grants/nhmrc/1090236 ARC |
Published version: | http://dx.doi.org/10.1084/jem.20160869 |
Appears in Collections: | Aurora harvest 4 Medical Sciences publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_121738.pdf | 3.26 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.