Abstract
Covalent attachment of ubiquitin, a small globular polypeptide, to protein substrates is a key post-translational modification that determines the fate, function, and turnover of most cellular proteins. Ubiquitin modification exists as mono- or polyubiquitin chains involving multiple ways how ubiquitin C-termini are connected to lysine, perhaps other amino acid side chains, and N-termini of proteins, often including branching of the ubiquitin chains. Understanding this enormous complexity in protein ubiquitination, the so-called ‘ubiquitin code’, in combination with the 1000 enzymes involved in controlling ubiquitin recognition, conjugation, and deconjugation, calls for novel developments in analytical techniques. Here, we review different headways in the field mainly driven by mass spectrometry and chemical biology, referred to as “ubiquitomics”, aiming to understand this system’s biological diversity.
Highlights
Protein ubiquitination is a post-translational modification (PTM) that involves the reversible attachment of ubiquitin to amino acid side chains, most commonly a lysine, on the target protein [1]
This review charts out recent progress that has been made in the field of ubiquitomics, and how these advances could help unravelling modes of ubiquitin modifications and subsequent biological effects
A ubiquitome refers to the set of proteins that are modified by ubiquitin and the associated ubiquitin chain topologies found under these conditions, it is not possible to determine both of these aspects in the same experiment
Summary
Protein ubiquitination is a post-translational modification (PTM) that involves the reversible attachment of ubiquitin to amino acid side chains, most commonly a lysine, on the target protein [1]. Ubiquitin was first named for its ubiquitous expression across eukaryotes [2]. This name is more apt than ever, with ubiquitin and ubiquitin-like proteins contributing to regulation of almost all aspects of cell activity [3]. The variety in ubiquitination signals is achieved through a large number of ubiquitin ligases and DUBs that present numerous modes of action. There are 2 E1 enzymes, ∼40 E2 enzymes, ∼600 E3 ligases [5], and just under 100 DUBs [6] in the human genome giving a large scope for potential modification by the different enzymes. E3 ligases can interact with more than one E2 [7] so there is vast potential for different E2/E3 pairs to target different substrates and assemble diverse polyubiquitin chain structures. This review charts out recent progress that has been made in the field of ubiquitomics, and how these advances could help unravelling modes of ubiquitin modifications and subsequent biological effects
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