Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival

Viant, C; Guia, S; Hennessy, RJ; Rautela, J; Pham, K; Bernat, C; Goh, W; Jiao, Y; Delconte, R; Roger, M; Simon, V; Souza-Fonseca-Guimaraes, F; Grabow, S; Belz, GT; Kile, BT; Strasser, A; Gray, D; Hodgkin, PD; Beutler, B; Vivier, E; Ugolini, S; Huntington, ND

Author(s): Viant, C; Guia, S; Hennessy, RJ; Rautela, J; Pham, K; Bernat, C; Goh, W; Jiao, Y; Delconte, R; Roger, M; Simon, V; Souza-Fonseca-Guimaraes, F; Grabow, S; Belz, GT; Kile, BT; Strasser, A; Gray, D; Hodgkin, PD; Beutler, B; Vivier, E; Ugolini, S; Huntington, ND;
Details: Publication Year 2017-02,Volume 214,Issue #2,Page 491-510
Journal Title: J Exp Med
Publication Type: Journal Article
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.
Publisher: Rockefeler Uni Press
Research Division(s): Immunology; Molecular Immunology; Chemical Biology; Molecular Genetics Of Cancer
PubMed ID: 28057804
Link To PubMed Central Version: https://www-ncbi-nlm-nih-gov/pmc/articles/PMC5294858/
Publisher's Version: https://doi.org/10.1084/jem.20160869
NHMRC Grants: NHMRC/1049407, NHMRC/1066770, NHMRC/1057852, NHMRC/1027472, NHMRC/1047903, NHMRC/1027472, NHMRC/1016701, NHMRC/1057831, NHMRC/1054925, NHMRC/10461276, NHMRC/1090236, NHMRC/1020363,
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Creation Date: 2017-04-06 09:27:16

Last Modified: 2017-08-21 11:49:06