ArticleProceedings of the National Academy of Sciences of the United States of America2021
Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- USP5 acts as a proteolytic switch to control SDE2 function via UBL-directed cleavage.Nature communications · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose.Nature communications · 2025Article
- Evolving role of deubiquitinating enzymes in oral cancer (Review).Oncology letters · 2025Review
- E2-Ub-R74G strategy reveals E2-specific ubiquitin conjugation profiles in live cells.Nature chemical biology · 2025Article
- The RBR E3 ubiquitin ligase HOIL-1 can ubiquitinate diverse non-protein substrates in vitro.Life science alliance · 2025Article
- Insights into non-proteinaceous ubiquitination.Biochemical Society transactions · 2025Review
- Ubiquitin is directly linked via an ester to protein-conjugated mono-ADP-ribose.The EMBO journal · 2025Article
- Insights into mechanisms of ubiquitin ADP-ribosylation reversal.Biochemical Society transactions · 2024Review
- VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.Nature structural & molecular biology · 2024Article
- Identification of new leads against ubiquitin specific protease-7 (USP7): a step towards the potential treatment of cancers.RSC advances · 2024Article
- Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L.EMBO reports · 2024Article
- Erasing marks: Functions of plant deubiquitylating enzymes in modulating the ubiquitin code.The Plant cell · 2024Review
- Specificity profiling of deubiquitylases against endogenously generated ubiquitin-protein conjugates.Cell chemical biology · 2024Article
- Bacterial esterases reverse lipopolysaccharide ubiquitylation to block host immunity.Cell host & microbe · 2024Article
- Preserving ester-linked modifications reveals glutamate and aspartate mono-ADP-ribosylation by PARP1 and its reversal by PARG.Nature communications · 2024Article
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Discovery and characterization of noncanonical E2-conjugating enzymes.Science advances · 2024Article
- The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases.The Biochemical journal · 2024Review
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Abstract
The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Here, we couple chemically and chemoenzymatically synthesized ubiquitinated lysine and threonine model substrates to a mass spectrometry-based DUB assay. Using this platform, we profile two-thirds of known catalytically active DUBs for threonine esterase and lysine isopeptidase activity and find that most DUBs demonstrate dual selectivity. However, with two anomalous exceptions, the ovarian tumor domain DUB class demonstrates specific (iso)peptidase activity. Strikingly, we find the Machado-Joseph disease (MJD) class to be unappreciated non-lysine DUBs with highly specific ubiquitin esterase activity rivaling the efficiency of the most active isopeptidases. Esterase activity is dependent on the canonical catalytic triad, but proximal hydrophobic residues appear to be general determinants of non-lysine activity. Our findings also suggest that ubiquitin esters have appreciable cellular stability and that non-lysine ubiquitination is an integral component of the ubiquitin system. Its regulatory sophistication is likely to rival that of canonical ubiquitination.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.