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Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression
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-κB by IL10 and CpG stimulation. W...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904148/ https://www.ncbi.nlm.nih.gov/pubmed/29666362 http://dx.doi.org/10.1038/s41467-018-03803-x |
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author | Feist, Maren Schwarzfischer, Philipp Heinrich, Paul Sun, Xueni Kemper, Judith von Bonin, Frederike Perez-Rubio, Paula Taruttis, Franziska Rehberg, Thorsten Dettmer, Katja Gronwald, Wolfram Reinders, Jörg Engelmann, Julia C. Dudek, Jan Klapper, Wolfram Trümper, Lorenz Spang, Rainer Oefner, Peter J. Kube, Dieter |
author_facet | Feist, Maren Schwarzfischer, Philipp Heinrich, Paul Sun, Xueni Kemper, Judith von Bonin, Frederike Perez-Rubio, Paula Taruttis, Franziska Rehberg, Thorsten Dettmer, Katja Gronwald, Wolfram Reinders, Jörg Engelmann, Julia C. Dudek, Jan Klapper, Wolfram Trümper, Lorenz Spang, Rainer Oefner, Peter J. Kube, Dieter |
author_sort | Feist, Maren |
collection | PubMed |
description | 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-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYC(low) cells depends on glutaminolysis. By (13)C- and (15)N-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-κB 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-κB 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. |
format | Online Article Text |
id | pubmed-5904148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59041482018-04-20 Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression Feist, Maren Schwarzfischer, Philipp Heinrich, Paul Sun, Xueni Kemper, Judith von Bonin, Frederike Perez-Rubio, Paula Taruttis, Franziska Rehberg, Thorsten Dettmer, Katja Gronwald, Wolfram Reinders, Jörg Engelmann, Julia C. Dudek, Jan Klapper, Wolfram Trümper, Lorenz Spang, Rainer Oefner, Peter J. Kube, Dieter Nat Commun Article 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-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYC(low) cells depends on glutaminolysis. By (13)C- and (15)N-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-κB 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-κB 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. Nature Publishing Group UK 2018-04-17 /pmc/articles/PMC5904148/ /pubmed/29666362 http://dx.doi.org/10.1038/s41467-018-03803-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Feist, Maren Schwarzfischer, Philipp Heinrich, Paul Sun, Xueni Kemper, Judith von Bonin, Frederike Perez-Rubio, Paula Taruttis, Franziska Rehberg, Thorsten Dettmer, Katja Gronwald, Wolfram Reinders, Jörg Engelmann, Julia C. Dudek, Jan Klapper, Wolfram Trümper, Lorenz Spang, Rainer Oefner, Peter J. Kube, Dieter Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression |
title | Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression |
title_full | Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression |
title_fullStr | Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression |
title_full_unstemmed | Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression |
title_short | Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression |
title_sort | cooperative stat/nf-κb signaling regulates lymphoma metabolic reprogramming and aberrant got2 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904148/ https://www.ncbi.nlm.nih.gov/pubmed/29666362 http://dx.doi.org/10.1038/s41467-018-03803-x |
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