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USP17-mediated de-ubiquitination and cancer: Clients cluster around the cell cycle

Ducker, Charles; Shaw, Peter E.

USP17-mediated de-ubiquitination and cancer: Clients cluster around the cell cycle Thumbnail


Peter E. Shaw


Eukaryotic cells perform a range of complex processes, some essential for life, others specific to cell type, all of which are governed by post-translational modifications of proteins. Among the repertoire of dynamic protein modifications, ubiquitination is arguably the most arcane and profound due to its complexity. Ubiquitin conjugation consists of three main steps, the last of which involves a multitude of target-specific ubiquitin ligases that conjugate a range of ubiquitination patterns to protein substrates with diverse outcomes. In contrast, ubiquitin removal is catalysed by a relatively small number of de-ubiquitinating enzymes (DUBs), which can also display target specificity and impact decisively on cell function. Here we review the current knowledge of the intriguing ubiquitin-specific protease 17 (USP17) family of DUBs, which are expressed from a highly copy number variable gene that has been implicated in multiple cancers, although available evidence points to conflicting roles in cell proliferation and survival. We show that key USP17 substrates populate two pathways that drive cell cycle progression and that USP17 activity serves to promote one pathway but inhibit the other. We propose that this arrangement enables USP17 to stimulate or inhibit proliferation depending on the mitogenic pathway that predominates in any given cell and may partially explain evidence pointing to both oncogenic and tumour suppressor properties of USP17.

Journal Article Type Review
Acceptance Date Nov 12, 2020
Online Publication Date Nov 20, 2020
Publication Date Jan 1, 2021
Deposit Date Dec 9, 2020
Publicly Available Date Nov 21, 2021
Journal The International Journal of Biochemistry & Cell Biology
Print ISSN 1357-2725
Electronic ISSN 1878-5875
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 130
Article Number 105886
Keywords Cell Biology; Biochemistry
Public URL
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