Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival
AuthorViant, C; Guia, S; Hennessy, RJ; Rautela, J; Pham, K; Bernat, C; Goh, W; Jiao, Y; Delconte, R; Roger, M; ...
Source TitleJournal of Experimental Medicine
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/sGray, Daniel; Belz, Gabrielle; Kile, Benjamin; Strasser, Andreas; Huntington, Nicholas; Grabow, Stephanie; Pham, Kim; Hodgkin, Philip; Delconte, Rebecca Beatrice; Rautela, Jai; ...
AffiliationMedical Biology (W.E.H.I.)
School of BioSciences
Document TypeJournal Article
CitationsViant, 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. ,... Huntington, N. D. (2017). Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival. JOURNAL OF EXPERIMENTAL MEDICINE, 214 (2), pp.491-510. https://doi.org/10.1084/jem.20160869.
Access StatusOpen Access
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.
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