| Literature DB >> 17618288 |
Nicholas D Huntington1, Hamsa Puthalakath, Priscilla Gunn, Edwina Naik, Ewa M Michalak, Mark J Smyth, Hyacinth Tabarias, Mariapia A Degli-Esposti, Grant Dewson, Simon N Willis, Noboru Motoyama, David C S Huang, Stephen L Nutt, David M Tarlinton, Andreas Strasser.
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.Entities:
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Year: 2007 PMID： 17618288 PMCID： PMC2951739 DOI： 10.1038/ni1487
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606