Alternative UPS drug targets upstream the 26S proteasome

The International Journal of Biochemistry & Cell Biology
Roland Hjerpe, Manuel S Rodríguez

Abstract

The successful use of proteasome inhibitors in anti-cancer therapy encouraged the development of new drugs targeting the activity of the ubiquitin-proteasome system (UPS) at various levels. The UPS comprises a complex set of protein adaptors whose coordinated function modulates the interaction of ubiquitin-modified proteins with protein effectors. In addition, UPS crosstalk with other post-translational modifications, complicates a sophisticated set of conjugation and de-conjugation pathways, providing a large variety of potential targets for the development of specific inhibitors. Traditionally associated with the proteasome, ubiquitin-conjugation does not always result in protein degradation. The major signal that targets proteins for degradation is the formation of ubiquitin-chains on lysine 48 (K48). Other ubiquitin features such as K63 chains or mono-ubiquitylation appear to regulate the transient formation of functional macromolecular complexes or relocate modified proteins inside the cell. The emerging idea that UPS-mediated degradation participates not only in the initiation but also in the termination step of certain functions, highlights new potential drug targets upstream the 26S proteasome. This review underlines so...Continue Reading

Citations

Nov 10, 2009·Seminars in Cancer Biology·Nerea Allende-Vega, Mark K Saville
Oct 20, 2009·European Journal of Pharmacology·Sudharsana Rao AndeSubbareddy Maddika
Sep 21, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Surinder M Soond, Andrew Chantry
Aug 16, 2014·Chembiochem : a European Journal of Chemical Biology·Min Jin KangEli Chapman
Jul 14, 2010·Bioorganic & Medicinal Chemistry·Harshani R LawrenceSaïd M Sebti
Mar 28, 2009·Nature·Daniela Hoeller, Ivan Dikic
Sep 17, 2008·Biochemical Society Transactions·Roland Hjerpe, Manuel S Rodríguez
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Litian ZhangLiang Chen
Oct 16, 2021·Experimental and Therapeutic Medicine·Fang ChengRunzhi He

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