Cell cycle progression dictates the requirement for BCL2 in natural killer cell survival
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
WEHI Research Division(s)
Immunology; Molecular Immunology; Chemical Biology; Molecular Genetics Of Cancer
PubMed ID
28057804
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-04-06 09:27:16
Last Modified: 2017-08-21 11:49:06
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