ArticleNature structural & molecular biology2024
VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators.The EMBO journal · 2026Article
- Interactions Between E3 Ubiquitin Ligases and Deubiquitinases in AKT Regulation: Implications in Skeletal Muscle Homeostasis.Cell biochemistry and function · 2026Review
- Unanchored ubiquitin chains promote the non-canonical inflammasome via UBXN1.Research square · 2026Article
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- The EF-hand domain of MINDY3 is a ubiquitin and RAD23 UBL-binding domain.EMBO reports · 2026Article
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- Article
- The many faces of p97/Cdc48 in mitochondrial homeostasis.Essays in biochemistry · 2025Review
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- The VCPKMT-VCP-HDAC1 axis inhibits colorectal cancer by conferring sensitivity to ferroptosis.Cancer cell international · 2025Article
- Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- ATXN3 regulates lysosome regeneration after damage by targeting K48-K63-branched ubiquitin chains.The EMBO journal · 2025Article
- The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks.Nucleic acids research · 2025Article
- Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains.Biochemical Society transactions · 2025Review
- The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025Review
- Insights into non-proteinaceous ubiquitination.Biochemical Society transactions · 2025Review
- UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains.Molecular cell · 2025Article
- Combinatorial ubiquitin code degrades deubiquitylation-protected substrates.Nature communications · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48-K63-branched Ub function. We establish a method to monitor cleavage of linkages within complex Ub chains and unveil ATXN3 and MINDY as debranching enzymes. We engineer a K48-K63 branch-specific nanobody and reveal the molecular basis of its specificity in crystal structures of nanobody-branched Ub chain complexes. Using this nanobody, we detect increased K48-K63-Ub branching following valosin-containing protein (VCP)/p97 inhibition and after DNA damage. Together with our discovery that multiple VCP/p97-associated proteins bind to or debranch K48-K63-linked Ub, these results suggest a function for K48-K63-branched chains in VCP/p97-related processes.
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Registered trials
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.