Kube, Dieter

[["dc.bibliographiccitation.artnumber","1514"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Feist, Maren"],["dc.contributor.author","Schwarzfischer, Philipp"],["dc.contributor.author","Heinrich, Paul"],["dc.contributor.author","Sun, Xueni"],["dc.contributor.author","Kemper, Judith"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Perez-Rubio, Paula"],["dc.contributor.author","Taruttis, Franziska"],["dc.contributor.author","Rehberg, Thorsten"],["dc.contributor.author","Dettmer, Katja"],["dc.contributor.author","Gronwald, Wolfram"],["dc.contributor.author","Reinders, Jörg"],["dc.contributor.author","Engelmann, Julia C."],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Trümper, Lorenz"],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Oefner, Peter J."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2019-07-09T11:45:23Z"],["dc.date.available","2019-07-09T11:45:23Z"],["dc.date.issued","2018"],["dc.description.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-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYClow cells depends on glutaminolysis. By 13C- and 15N-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."],["dc.identifier.doi","10.1038/s41467-018-03803-x"],["dc.identifier.pmid","29666362"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15191"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59220"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2041-1723"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","571"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Oncology"],["dc.bibliographiccitation.lastpage","589"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Arlt, Annekatrin"],["dc.contributor.author","Bonin, Frederike"],["dc.contributor.author","Rehberg, Thorsten"],["dc.contributor.author","Perez‐Rubio, Paula"],["dc.contributor.author","Engelmann, Julia C."],["dc.contributor.author","Limm, Katharina"],["dc.contributor.author","Reinke, Sarah"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Sun, Xueni"],["dc.contributor.author","Specht, Rieke"],["dc.contributor.author","Maulhardt, Markus"],["dc.contributor.author","Linke, Franziska"],["dc.contributor.author","Bunt, Gertrude"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dettmer, Katja"],["dc.contributor.author","Gronwald, Wolfram"],["dc.contributor.author","Oefner, Peter J."],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2021-04-14T08:27:44Z"],["dc.date.available","2021-04-14T08:27:44Z"],["dc.date.issued","2020"],["dc.description.abstract","Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination."],["dc.description.abstract","The study highlights the ability of Hodgkin lymphoma cells to attract and to differentiate monocytes into M2‐like Mφ and the role of IL13 in regulating CD206 but also that CD206 contributes to the remodeling of the tumor microenvironment via take up glycoconjugates as well as type‐I collagen and immunosuppression by PD‐L1 upregulation. image"],["dc.description.sponsorship","Stiftung der Georg‐August‐Universität"],["dc.description.sponsorship","Wilhelm‐Sander‐Stiftung"],["dc.description.sponsorship","Deutsche Krebshilfe http://dx.doi.org/10.13039/501100005972"],["dc.description.sponsorship","Bundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347"],["dc.description.sponsorship","Interreg"],["dc.identifier.doi","10.1002/1878-0261.12616"],["dc.identifier.eissn","1878-0261"],["dc.identifier.issn","1574-7891"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17183"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82387"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1878-0261"],["dc.relation.issn","1574-7891"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47061"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","47081"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Meyer, Katharina"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Stolz, Ailine"],["dc.contributor.author","Feist, Maren"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Evers, Maurits"],["dc.contributor.author","Kohler, Christian W."],["dc.contributor.author","Shirneshan, Katayoon"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Szczepanowski, Monika"],["dc.contributor.author","Murray, Paul G."],["dc.contributor.author","Bastians, Holger"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T10:11:28Z"],["dc.date.available","2018-11-07T10:11:28Z"],["dc.date.issued","2016"],["dc.description.abstract","To discover new regulatory pathways in B lymphoma cells, we performed a combined analysis of experimental, clinical and global gene expression data. We identified a specific cluster of genes that was coherently expressed in primary lymphoma samples and suppressed by activation of the B cell receptor (BCR) through aIgM treatment of lymphoma cells in vitro. This gene cluster, which we called BCR. 1, includes numerous cell cycle regulators. A reduced expression of BCR. 1 genes after BCR activation was observed in different cell lines and also in CD10(+) germinal center B cells. We found that BCR activation led to a delayed entry to and progression of mitosis and defects in metaphase. Cytogenetic changes were detected upon long-term aIgM treatment. Furthermore, an inverse correlation of BCR. 1 genes with c-Myc co-regulated genes in distinct groups of lymphoma patients was observed. Finally, we showed that the BCR. 1 index discriminates activated B cell-like and germinal centre B cell-like diffuse large B cell lymphoma supporting the functional relevance of this new regulatory circuit and the power of guided clustering for biomarker discovery."],["dc.identifier.doi","10.18632/oncotarget.9219"],["dc.identifier.isi","000385413000020"],["dc.identifier.pmid","27166259"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14137"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40052"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","893"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Bioinformatics"],["dc.bibliographiccitation.lastpage","900"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Pirkl, Martin"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Spang, Rainer"],["dc.date.accessioned","2018-11-07T10:16:48Z"],["dc.date.available","2018-11-07T10:16:48Z"],["dc.date.issued","2016"],["dc.description.abstract","Motivation: Understanding the structure and interplay of cellular signalling pathways is one of the great challenges in molecular biology. Boolean Networks can infer signalling networks from observations of protein activation. In situations where it is difficult to assess protein activation directly, Nested Effect Models are an alternative. They derive the network structure indirectly from downstream effects of pathway perturbations. To date, Nested Effect Models cannot resolve signalling details like the formation of signalling complexes or the activation of proteins by multiple alternative input signals. Here we introduce Boolean Nested Effect Models (B-NEM). B-NEMs combine the use of downstream effects with the higher resolution of signalling pathway structures in Boolean Networks. Results: We show that B-NEMs accurately reconstruct signal flows in simulated data. Using B-NEM we then resolve BCR signalling via PI3K and TAK1 kinases in BL2 lymphoma cell lines."],["dc.description.sponsorship","Bavarian Research Network for Molecular Biosystems (BioSysNet)"],["dc.identifier.doi","10.1093/bioinformatics/btv680"],["dc.identifier.isi","000372975000013"],["dc.identifier.pmid","26581413"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13405"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41107"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2059"],["dc.relation.issn","1367-4803"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]