Natural products as inhibitorsof the ubiquitin-/ubiquitin-likeprotein-proteasome pathway

Edmond Dik Lung Ma*, Victor Pui-Yan Ma, Daniel Shiu-Hin Chan, Ka Ho Leung, Hai Jing Zhong, Chung Hang Leung

*Corresponding author for this work

Research output: Chapter in book/report/conference proceedingChapterpeer-review


The proteasome is the final player in the regulated degradation of intracellularproteins through in both ubiquitin-dependent and ubiquitin-independent proteolyticpathways. In eukaryotic cells, the ubiquitin-proteasome system coordinates thepolyubiquitination and subsequent proteolysis of unwanted proteins, crucial to normalcellular homeostasis. The first-in-class proteasome inhibitor, bortezomib. promotesapoptosis and chemosensitization of cancer cells, and is used clinically as either a singleagentchemotherapeutic or in combination with other drugs. Natural products offermedicinal chemists with a cornucopia of diverse chemical scaffolds and bioactivesubstructures, and historically have represented an important source of new drugs.Salinosporamide A (NPI-0052), a second-generation proteasome inhibitor of marinemicrobial origin, has been effective against bortezomib-resistant cancers and has enteredPhase I clinical trials. This review discusses the application of natural products asinhibitors of the ubiquitin-proteasome system through targeting of both conventional proteolytic pathways as well as those involving ubiquitin-like proteins, such as NEDD8,which have recently emerged as novel anti-cancer targets.

Original languageEnglish
Title of host publicationNatural Products
Subtitle of host publicationStructure, Bioactivity and Applications
PublisherNova Science Publishers
Number of pages20
ISBN (Print)9781620817285
Publication statusPublished - Oct 2012

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)


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