ArticleNature chemical biology2025
E2-Ub-R74G strategy reveals E2-specific ubiquitin conjugation profiles in live cells.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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Who cites it
3 citing papers in PubMed.
- UBE2L6 drives ulcerative colitis progression by promoting BIRC2 degradation and activating non-canonical NF-κB signalling.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Mechanistic basis for protein conjugation in a diverged bacterial ubiquitination pathway.Nature structural & molecular biology · 2026Article
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
The E2 ubiquitin (Ub)-conjugating enzyme primarily determines Ub conjugation as Ub-isopeptide (lysine), Ub-oxyester (serine/threonine) or Ub-thioester (cysteine). However, E2-specific Ub conjugation profiles within cells remain elusive. Here we developed the fusion E2-Ub-R74G profiling (FUSEP) strategy to access E2-specific Ub conjugation profiles in cells with amino acid resolution. The probe-specific leucine-glycine-glycine-glycine-modified Ub remnant enables systematic studies of non-lysine Ub conjugation and provides site-specific information. Multiple E2 enzymes were found to be involved in non-lysine ubiquitination. Profiling with UBE2D3-Ub-R74G probes identified a post-translational modification, tyrosine ubiquitination, in human Cullin-1, a scaffold protein for Cullin-RING E3 Ub ligases. This modification is distinct from lysine ubiquitination. A single-pass membrane-bound E3 ligase, RNF149, was identified to pair with UBE2D3 to regulate pyroptosis by ubiquitinating apoptosis-associated speck-like protein ASC. The availability of this toolbox paves the way for uncovering E2-specific Ub conjugation profiles and identifying previously unknown E3 Ub ligases for potential therapeutic applications.
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Identifiers
39762535What OpenQuestion holds
Registered trials
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