ArticleeLife2022
Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.
Article in eLife, 2022. 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, 30 citations in OpenAlex.
- 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
- FAF1 cofactor enhances UFD1/NPL4-p97 unfolding efficiency across ubiquitin chain lengths independent of SUMO2.bioRxiv : the preprint server for biology · 2026Article
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.Cell reports · 2026Article
- The p97 adaptor p47/NSFL1C is necessary for stress granule dissolution after heat stress.bioRxiv : the preprint server for biology · 2026Article
- The accessory adapters FAF1, FAF2, and UBXN7 accelerate proteasomal degradation by increasing prior p97-mediated substrate unfolding.Science advances · 2026Article
- A UBH-UBX module amplifies p97/VCP's unfolding power to facilitate protein extraction and degradation.Nature communications · 2025Article
- Faf1 accelerates p97-mediated protein unfolding by promoting ubiquitin engagement.bioRxiv : the preprint server for biology · 2025Article
- The p97 ATPase and its adaptor UBXD8 maintain peroxisome pools by preventing pexophagy.The Journal of cell biology · 2025Article
- p97/VCP is required for piecemeal autophagy of aggresomes.Nature communications · 2025Article
- Elucidation of the late steps in the glycan-dependent ERAD of soluble misfolded glycoproteins.The Plant journal : for cell and molecular biology · 2025Article
- AAA+ ATPase chaperone p97/VCPNature communications · 2024Article
- Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation.Molecular cell · 2024Article
- Review
- VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates.Nature communications · 2024Article
- DONSON is required for CMG helicase assembly in the mammalian cell cycle.EMBO reports · 2023Article
- Ubiquitin-Dependent and Independent Proteasomal Degradation in Host-Pathogen Interactions.Molecules (Basel, Switzerland) · 2023Review
- Article
- Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast.The EMBO journal · 2023Article
- A protein-lipid complex that detoxifies free fatty acids.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
The p97/Cdc48 ATPase and its ubiquitin receptors Ufd1-Npl4 are essential to unfold ubiquitylated proteins in many areas of eukaryotic cell biology. In yeast, Cdc48-Ufd1-Npl4 is controlled by a quality control mechanism, whereby substrates must be conjugated to at least five ubiquitins. Here, we show that mammalian p97-UFD1-NPL4 is governed by a complex interplay between additional p97 cofactors and the number of conjugated ubiquitins. Using reconstituted assays for the disassembly of ubiquitylated CMG (Cdc45-MCM-GINS) helicase by human p97-UFD1-NPL4, we show that the unfoldase has a high ubiquitin threshold for substrate unfolding, which can be reduced by the UBX proteins UBXN7, FAF1, or FAF2. Our data indicate that the UBX proteins function by binding to p97-UFD1-NPL4 and stabilising productive interactions between UFD1-NPL4 and K48-linked chains of at least five ubiquitins. Stimulation by UBXN7 is dependent upon known ubiquitin-binding motifs, whereas FAF1 and FAF2 use a previously uncharacterised coiled-coil domain to reduce the ubiquitin threshold of p97-UFD1-NPL4. We show that deleting the
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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.