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Gorelik M, Sidhu SS. Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants. Bioeng Transl Med. 2016;2(1):31-42doi: 10.1002/btm2.10044.
Gorelik, M., & Sidhu, S. S. (2017). Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants. Bioengineering & translational medicine, 2(1), 31-42. https://doi.org/10.1002/btm2.10044
Gorelik, Maryna, and Sidhu, Sachdev S. "Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants." Bioengineering & translational medicine vol. 2,1 (2017): 31-42. doi: https://doi.org/10.1002/btm2.10044
Gorelik M, Sidhu SS. Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants. Bioeng Transl Med. 2017 Mar;2(1):31-42. doi: 10.1002/btm2.10044. Epub 2016 Nov 14. PMID: 28580429; PMCID: PMC5434665.
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Bioeng Transl Med. 2017 Mar;2(1):31-42. doi: 10.1002/btm2.10044. Epub 2016 Nov 14.

Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants.

Bioengineering & translational medicine

Maryna Gorelik, Sachdev S Sidhu

Affiliations

  1. Banting and Best Dept. of Medical Research and the Dept. of Molecular Genetics Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto 160 College Street Toronto ON Canada M5S 3E1.

PMID: 28580429 PMCID: PMC5434665 DOI: 10.1002/btm2.10044

Abstract

The ubiquitin proteasome system (UPS) has garnered much attention due to its potential for the development of therapeutics. Following a successful clinical application of general proteasome inhibitors much effort has been devoted to targeting individual UPS components including E3 enzymes and deubiquitinases that control specificity of ubiquitination. Our group has developed a novel approach for targeting the UPS proteins using engineered ubiquitin variants (Ubvs). These drug-like proteins can serve as valuable tools to study biological function of UPS components and assist in the development of small molecules for clinical use. In this review, we summarize studies of Ubvs targeting members of three major families, including deubiquitinases, HECT E3 ligases, and CRL E3 ligases. In particular, we focus on Ubv binding mechanisms, structural studies, and effects on enzyme function. Furthermore, new insights gained from the Ubvs are discussed in the context of small molecule studies.

Keywords: APC/C; DUBs; SCF E3 ligases; phage display; protein engineering; small protein scaffolds

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