Loftus, Roisin M. and Assmann, Nadine and Kedia-Mehta, Nidhi and O'Brien, Katie L. and Garcia, Arianne and Gillespie, Conor and Hukelmann, Jens L. and Oefner, Peter J. and Lamond, Angus and Gardiner, Clair M. and Dettmer, Katja and Cantrell, Doreen A. and Sinclair, Linda and Finlay, David K. (2018) Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice. NATURE COMMUNICATIONS, 9: 2341. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked. We identify SLC7A5 as the predominant system L-amino acid transporter in activated NK cells. Unlike other lymphocyte subsets, glutaminolysis and the tricarboxylic acid cycle do not sustain OXPHOS in activated NK cells. Glutamine withdrawal, but not the inhibition of glutaminolysis, results in the loss of cMyc protein, reduced cell growth and impaired NK cell responses. These data identify an essential role for amino acid-controlled cMyc for NK cell metabolism and function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-LYMPHOCYTE ACTIVATION; NATURAL-KILLER-CELLS; C-MYC PROTEOLYSIS; B-CELLS; ANTIBODY-PRODUCTION; GLUCOSE-METABOLISM; GLUTAMINE; CANCER; PATHWAY; DIFFERENTIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2020 09:56 |
| Last Modified: | 09 Mar 2020 09:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14400 |
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