- Titel
- YB-1 Interferes with TNF–TNFR Binding and Modulates Progranulin-Mediated Inhibition of TNF Signaling
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-896384
- Quellenangabe
- International Journal of Molecular Sciences
Erscheinungsjahr: 2020
Jahrgang: 21
Artikelnummer: 7076 - Erstveröffentlichung
- 2020
- Abstract (EN)
- 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 amplifying the cytokine network. Progranulin (PGRN) is a growth factor that binds to TNF receptors and interferes with TNF-mediated signaling. Extracellular PGRN is processed into granulins by proteases released from 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-box binding protein-1 (YB-1) as a candidate for this immune-modulating activity. Using a yeast-2-hybrid assay with YB-1 protein as bait, clones encoding for progranulin were selected using stringent criteria for strong interaction. We demonstrate that at physiological concentrations, YB-1 interferes with the binding of TNF to its receptors in a dose-dependent manner using a flow cytometry-based binding assay. We show that YB-1 in combination with progranulin interferes with TNF-mediated signaling, supporting the functionality with an NF-B luciferase reporter assay. Together, we show that YB-1 displays immunomodulating functions by affecting the binding of TNF to its receptors and influencing TNF-mediated signaling via its interaction with progranulin.
- Andere Ausgabe
- Link zur Erstveröffentlichung
Link: https://doi.org/10.3390/ijms21197076 - Freie Schlagwörter (EN)
- Y-box binding protein-1 (YB-1); DNA binding protein-B (DbpB); progranulin; tumor necrosis factor alpha (TNF); inflammation; immune modulation; signaling; macrophage
- Klassifikation (DDC)
- 610
- Verlag
- MDPI, Basel
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-896384
- Veröffentlichungsdatum Qucosa
- 09.02.2024
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0