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

Simple item page
dc.contributor.authorViant, C.
dc.contributor.authorGuia, S.
dc.contributor.authorHennessy, R.J.
dc.contributor.authorRautela, J.
dc.contributor.authorPham, K.
dc.contributor.authorBernat, C.
dc.contributor.authorGoh, W.
dc.contributor.authorJiao, Y.
dc.contributor.authorDelconte, R.
dc.contributor.authorRoger, M.
dc.contributor.authorSimon, V.
dc.contributor.authorSouza-Fonseca-Guimaraes, F.
dc.contributor.authorGrabow, S.
dc.contributor.authorBelz, G.T.
dc.contributor.authorKile, B.T.
dc.contributor.authorStrasser, A.
dc.contributor.authorGray, D.
dc.contributor.authorHodgkin, P.D.
dc.contributor.authorBeutler, B.
dc.contributor.authorVivier, E.
dc.contributor.authoret al.
dc.date.issued2017
dc.description.abstractNatural 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.
dc.description.statementofresponsibilityCharlotte Viant, Sophie Guia, Robert J. Hennessy, Jai Rautela, Kim Pham ... Benjamin T. Kile ... et al.
dc.identifier.citationJournal of Experimental Medicine (JEM), 2017; 214(2):491-510
dc.identifier.doi10.1084/jem.20160869
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.orcidKile, B.T. [0000-0002-8836-8947]
dc.identifier.urihttp://hdl.handle.net/2440/121738
dc.language.isoen
dc.publisherRockefeller University Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1049407
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1066770
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1057852
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1027472
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1047903
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1078763
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016701
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1057831
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1054925
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/0461276
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1020363
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1090236
dc.relation.grantARC
dc.rights© 2017 Viant et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http ://www .rupress .org /terms /). After six months it is available under a Creative Commons License (Attribution–Noncommercial– Share Alike 4.0 International license, as described at https ://creativecommons .org /licenses /by -nc -sa /4 .0 /).
dc.source.urihttps://doi.org/10.1084/jem.20160869
dc.subjectKiller Cells, Natural
dc.titleCell cycle progression dictates the requirement for BCL2 in natural killer cell survival
dc.typeJournal article
pubs.publication-statusPublished

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
hdl_121738.pdf
Size:
3.18 MB
Format:
Adobe Portable Document Format
Download

Collections

Medical Sciences publications