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Hessmann, Christopher L. [VerfasserIn]; Hildebrandt, Josephine [VerfasserIn]; Shah, Aneri [VerfasserIn]; Brandt, Sabine [VerfasserIn]; Bock, Antonia [VerfasserIn]; Frye, Björn C. [VerfasserIn]; Raffetseder, Ute [VerfasserIn]; Geffers, Robert [VerfasserIn]; Brunner-Weinzierl, Monika C. [VerfasserIn]; Isermann, Berend [VerfasserIn]; Mertens, Peter R. [VerfasserIn]; Lindquist, Jonathan A. [VerfasserIn]

YB-1 Interferes with TNF–TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNF Signaling

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  • Medientyp: E-Artikel
  • Titel: YB-1 Interferes with TNF–TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNF Signaling
  • Beteiligte: Hessmann, Christopher L. [VerfasserIn]; Hildebrandt, Josephine [VerfasserIn]; Shah, Aneri [VerfasserIn]; Brandt, Sabine [VerfasserIn]; Bock, Antonia [VerfasserIn]; Frye, Björn C. [VerfasserIn]; Raffetseder, Ute [VerfasserIn]; Geffers, Robert [VerfasserIn]; Brunner-Weinzierl, Monika C. [VerfasserIn]; Isermann, Berend [VerfasserIn]; Mertens, Peter R. [VerfasserIn]; Lindquist, Jonathan A. [VerfasserIn]
  • Erschienen: Basel: MDPI, [2024]
  • Erschienen in: International Journal of Molecular Sciences ; 21, (2020)
  • Sprache: Englisch
  • Schlagwörter: tumor necrosis factor alpha (TNF) ; signaling ; inflammation ; Y-box binding protein-1 (YB-1) ; DNA binding protein-B (DbpB) ; macrophage ; immune modulation ; progranulin
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Inflammation and an influx of macrophages are common elements in many diseases.Among pro-inflammatory cytokines, tumor necrosis factor(TNF) plays a central role by amplifyingthe cytokine network. Progranulin (PGRN) is a growth factor that binds to TNF receptors and interfereswith TNF-mediated signaling. Extracellular PGRN is processed into granulins by proteases releasedfrom immune cells. PGRN exerts anti-inflammatory effects, whereas granulins are pro-inflammatory.The factors coordinating these ambivalent functions remain unclear. In our study, we identify Y-boxbinding protein-1 (YB-1) as a candidate for this immune-modulating activity. Using a yeast-2-hybridassay with YB-1 protein as bait, clones encoding for progranulin were selected using stringent criteriafor strong interaction. We demonstrate that at physiological concentrations, YB-1 interferes withthe binding of TNF to its receptors in a dose-dependent manner using a flow cytometry-basedbinding assay. We show that YB-1 in combination with progranulin interferes with TNF-mediatedsignaling, supporting the functionality with an NF-B luciferase reporter assay. Together, we showthat YB-1 displays immunomodulating functions by affecting the binding of TNF to its receptorsand influencing TNF-mediated signaling via its interaction with progranulin.
  • Zugangsstatus: Freier Zugang
  • Rechte-/Nutzungshinweise: Namensnennung (CC BY)