ArticleCell communication and signaling : CCS2023
The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 7 citations in OpenAlex.
- A gut commensalVirulence · 2026Article
- Prodigiosin in glioblastoma: mechanistic pharmacology and rationale for its development as a radiosensitiser.Frontiers in pharmacology · 2026Review
- The Polybrominated Diphenyl Ether Bromoxib Disrupts Nuclear Import and Export by Affecting Nucleoporins of the Nuclear Pore Complex.Marine drugs · 2025Article
- Targeting mitochondrial metabolism by the mitotoxin bromoxib in leukemia and lymphoma cells.Cell communication and signaling : CCS · 2024Article
- The Golgi Apparatus as an Anticancer Therapeutic Target.Biology · 2023Review
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Authors and funding
13 authors at 2 institutions in 1 country.
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Abstract
backgroundThe 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.
methodsWe 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.
resultsWe 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.
conclusionTaken 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. Video Abstract.
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