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Mar. Drugs 2018, 16(12), 467; https://doi.org/10.3390/md16120467

Clogging the Ubiquitin-Proteasome Machinery with Marine Natural Products: Last Decade Update

1
Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
2
The NeaNat Group, Department of Pharmacy, University of Naples Federico II, via D. Montesano 49, 80131 Napoli, Italy
3
Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100 Foggia, Italy
*
Authors to whom correspondence should be addressed.
Received: 26 October 2018 / Revised: 11 November 2018 / Accepted: 22 November 2018 / Published: 26 November 2018
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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 and misfolded (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. View Full-Text
Keywords: natural products; ubiquitin; proteasome; marine; salinosporamide; cancer; high-throughput screening; secondary metabolites; lead compounds natural products; ubiquitin; proteasome; marine; salinosporamide; cancer; high-throughput screening; secondary metabolites; lead compounds
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Della Sala, G.; Agriesti, F.; Mazzoccoli, C.; Tataranni, T.; Costantino, V.; Piccoli, C. Clogging the Ubiquitin-Proteasome Machinery with Marine Natural Products: Last Decade Update. Mar. Drugs 2018, 16, 467.

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