Clogging the ubiquitin-proteasome machinery with marine natural products: Last decade update

Gerardo Della Sala, Francesca Agriesti, Carmela Mazzoccoli, Tiziana Tataranni, Valeria Costantino, Claudia Piccoli

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

The ubiquitin-proteasome pathway (UPP) is the central protein degradation system in eukaryotic cells, playing a key role in homeostasis maintenance, through proteolysis of regulatory andmisfolded (potentially harmful) proteins. As cancer cells produce proteins inducing cell proliferation and inhibiting cell death pathways, UPP inhibition has been exploited as an anticancer strategy to shift the balance between protein synthesis and degradation towards cell death. Over the last few years, marine invertebrates and microorganisms have shown to be an unexhaustive factory of secondary metabolites targeting the UPP. These chemically intriguing compounds can inspire clinical development of novel antitumor drugs to cope with the incessant outbreak of side effects and resistance mechanisms induced by currently approved proteasome inhibitors (e.g., bortezomib). In this review, we report about (a) the role of the UPP in anticancer therapy, (b) chemical and biological properties of UPP inhibitors from marine sources discovered in the last decade, (c) high-throughput screening techniques for mining natural UPP inhibitors in organic extracts. Moreover, we will tell about the fascinating story of salinosporamide A, the first marine natural product to access clinical trials as a proteasome inhibitor for cancer treatment.

Original languageEnglish
Article number467
JournalMarine Drugs
Volume16
Issue number12
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Proteasome Endopeptidase Complex
Ubiquitin
Biological Products
Proteasome Inhibitors
Proteolysis
Cell Death
Eukaryotic Cells
Invertebrates
Antineoplastic Agents
Disease Outbreaks
Neoplasms
Proteins
Homeostasis
Maintenance
Cell Proliferation
Clinical Trials

Keywords

  • Cancer
  • High-throughput screening
  • Lead compounds
  • Marine
  • Natural products
  • Proteasome
  • Salinosporamide
  • Secondary metabolites
  • Ubiquitin

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Sala, G. D., Agriesti, F., Mazzoccoli, C., Tataranni, T., Costantino, V., & Piccoli, C. (2018). Clogging the ubiquitin-proteasome machinery with marine natural products: Last decade update. Marine Drugs, 16(12), [467]. https://doi.org/10.3390/md16120467

Clogging the ubiquitin-proteasome machinery with marine natural products : Last decade update. / Sala, Gerardo Della; Agriesti, Francesca; Mazzoccoli, Carmela; Tataranni, Tiziana; Costantino, Valeria; Piccoli, Claudia.

In: Marine Drugs, Vol. 16, No. 12, 467, 01.01.2018.

Research output: Contribution to journalReview article

Sala, GD, Agriesti, F, Mazzoccoli, C, Tataranni, T, Costantino, V & Piccoli, C 2018, 'Clogging the ubiquitin-proteasome machinery with marine natural products: Last decade update', Marine Drugs, vol. 16, no. 12, 467. https://doi.org/10.3390/md16120467
Sala GD, Agriesti F, Mazzoccoli C, Tataranni T, Costantino V, Piccoli C. Clogging the ubiquitin-proteasome machinery with marine natural products: Last decade update. Marine Drugs. 2018 Jan 1;16(12). 467. https://doi.org/10.3390/md16120467
Sala, Gerardo Della ; Agriesti, Francesca ; Mazzoccoli, Carmela ; Tataranni, Tiziana ; Costantino, Valeria ; Piccoli, Claudia. / Clogging the ubiquitin-proteasome machinery with marine natural products : Last decade update. In: Marine Drugs. 2018 ; Vol. 16, No. 12.
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