Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1
Details
Publication Year 2007-08, Volume 8, Issue #8, Page 856-863
Journal Title
NATURE IMMUNOLOGY
Publication Type
Journal Article
Abstract
Interleukin 15 (IL-15) promotes the survival of natural killer (NK) cells by preventing apoptosis through mechanisms unknown at present. Here we identify Bim, Noxa and Mcl-1 as key regulators of IL-15-dependent survival of NK cells. IL-15 suppressed apoptosis by limiting Bim expression through the kinases Erk1 and Erk2 and mechanisms dependent on the transcription factor Foxo3a, while promoting expression of Mcl-1, which was necessary and sufficient for the survival of NK cells. Withdrawal of IL-15 led to upregulation of Bim and, accordingly, both Bim-deficient and Foxo3a(-/-) NK cells were resistant to cytokine deprivation. Finally, IL-15-mediated inactivation of Foxo3a and cell survival were dependent on phosphotidylinositol-3-OH kinase. Thus, IL-15 regulates the survival of NK cells at multiple steps, with Bim and Noxa being key antagonists of Mcl-1, the critical survivor factor in this process.
Publisher
NATURE PUBLISHING GROUP
Keywords
FORKHEAD TRANSCRIPTION FACTOR; FAMILY-MEMBER BIM; BCL-2 FAMILY; BH3-ONLY PROTEINS; LYMPHOID DEVELOPMENT; APOPTOTIC RESPONSES; DEFICIENT MICE; FACTOR FKHR-L1; B-CELL; HOMEOSTASIS
Publisher's Version
https://doi.org/10.1038/ni1487
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2007-08-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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