Feist, Maren and Schwarzfischer, Philipp and Heinrich, Paul and Sun, Xueni and Kemper, Judith and von Bonin, Frederike and Perez-Rubio, Paula and Taruttis, Franziska and Rehberg, Thorsten and Dettmer, Katja and Gronwald, Wolfram and Reinders, Joerg and Engelmann, Julia C. and Dudek, Jan and Klapper, Wolfram and Truemper, Lorenz and Spang, Rainer and Oefner, Peter J. and Kube, Dieter (2018) Cooperative STAT/NF-kappa B signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression. NATURE COMMUNICATIONS, 9: 1514. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Knowledge of stromal factors that have a role in the transcriptional regulation of metabolic pathways aside from c-Myc is fundamental to improvements in lymphoma therapy. Using a MYC-inducible human B-cell line, we observed the cooperative activation of STAT3 and NF-kappa B by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYClow cells depends on glutaminolysis. By C-13- and N-15-tracing of glutamine metabolism and metabolite rescue experiments, we demonstrate that GOT2 provides aspartate and nucleotides to cells with activated or aberrant Jak/STAT and NF-kappa B signaling. A model of GOT2 transcriptional regulation is proposed, in which the cooperative phosphorylation of STAT3 and direct joint binding of STAT3 and p65/NF-kappa B to the proximal GOT2 promoter are important. Furthermore, high aberrant GOT2 expression is prognostic in diffuse large B-cell lymphoma underscoring the current findings and importance of stromal factors in lymphoma biology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL LYMPHOMA; GLUTAMINE-METABOLISM; BREAST-CANCER; C-MYC; HODGKIN LYMPHOMA; GENE-EXPRESSION; GLUCOSE-UPTAKE; ACTIVATION; PROLIFERATION; PATHWAY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 07:27 |
| Last Modified: | 20 Mar 2020 07:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14719 |
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