Dokument: The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin
| Titel: | The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=67529 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20241115-091131-4 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Berning, Lena [Autor] Lenz, Thomas [Autor] Bergmann, Ann Kathrin [Autor] Poschmann, Gereon [Autor] Brass, Hannah U.C. [Autor] Schlütermann, David [Autor] Friedrich, Annabelle [Autor] Mendiburo, María José [Autor] David, Céline [Autor] Akgün, Seda [Autor] | |||||||
| Dateien: |
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| Stichwörter: | Natural compound, Target identification, Prodigiosin, Golgi apparatus, Autophagy | |||||||
| Beschreibung: | Background
The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified. Methods We used mass spectrometry-based thermal proteome profiling in order to identify target proteins of prodigiosin. For target validation, we employed a genetic knockout approach and electron microscopy. Results We identified the Golgi stacking protein GRASP55 as target protein of prodigiosin. We show that prodigiosin treatment severely affects Golgi morphology and functionality, and that prodigiosin-dependent cytotoxicity is partially reduced in GRASP55 knockout cells. We also found that prodigiosin treatment results in decreased cathepsin activity and overall blocks autophagic flux, whereas co-localization of the autophagosomal marker LC3 and the lysosomal marker LAMP1 is clearly promoted. Finally, we observed that autophagosomes accumulate at GRASP55-positive structures, pointing towards an involvement of an altered Golgi function in the autophagy-inhibitory effect of this natural compound. Conclusion Taken together, we propose that prodigiosin affects autophagy and Golgi apparatus integrity in an interlinked mode of action involving the regulation of organelle alkalization and the Golgi stacking protein GRASP55. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Berning, L., Lenz, T., Bergmann, A. K., Poschmann, G., Braß, H., Schlütermann, D., Friedrich, A., Mendiburo, M.-J., David, C., Akgün, S., Pietruszka, J., Stühler, K., & Stork, B. (2023). The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin. Cell Communication and Signaling, 21, Article 275. https://doi.org/10.1186/s12964-023-01275-1 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät Medizinische Fakultät | |||||||
| Dokument erstellt am: | 15.11.2024 | |||||||
| Dateien geändert am: | 15.11.2024 |
