Abstract
Protein ubiquitination is a key post-translational modification that regulates diverse cellular processes in eukaryotic cells. The specificity of ubiquitin (Ub) signalling for different bioprocesses and pathways is dictated by the large variety of mono-ubiquitination and polyubiquitination events, including many possible chain architectures. Deubiquitinases (DUBs) reverse or edit Ub signals with high sophistication and specificity, forming an integral arm of the Ub signalling machinery, thus impinging on fundamental cellular processes including DNA damage repair, gene expression, protein quality control and organellar integrity. In this review, we discuss the many layers of DUB function and regulation, with a focus on insights gained from budding yeast. Our review provides a framework to understand key aspects of DUB biology.
Highlights
Ubiquitination is a reversible post-translational modification (PTM) that governs a wide variety of cellular processes including protein degradation and sorting, cell signalling and gene expression [1]
The roster of DUBs encoded by the human genome is more extensive with approximately 100 DUBs that are divided into seven families: the ubiquitin-specific proteases (USP/UBP); ubiquitin C-terminal hydrolases (UCHs); ovarian tumour proteases (OTUs); JAB1/MPN/ MOV34s (JAMMs); Josephins, zinc finger with UFM1-specific peptidase domain protein protease (ZUFSP) and the recently discovered MINDY
Five of the seven DUB families (USP/UBP, UCH, OTU, JAMM and MINDY) are conserved in yeast [11,12,13], and below we summarize our understanding of the functions and mechanisms of action of these conserved DUB families
Summary
Ubiquitination is a reversible post-translational modification (PTM) that governs a wide variety of cellular processes including protein degradation and sorting, cell signalling and gene expression [1]. DUBs have three major cellular functions: (i) the generation of free Ub moieties from linear fusions of Ub [1,2,3,4,5]; (ii) trimming of existing polyubiquitin chains; and (iii) reversal of Ub signalling by removal of Ub chains from target proteins [1,2,3,4,5]. Owing to the importance of DUBs in eukaryotic cell biology, there has been a concerted effort to understand their structure, mechanisms of substrate and polyubiquitin chain-type recognition and modes of regulation. Key insights into DUB biology have emerged from work in model organisms such as the budding yeast, Saccharomyces cerevisiae. From work in yeast for understanding DUB function in more complex organisms such as humans
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