ArticleMolecular cell2023
The Ufd1 cofactor determines the linkage specificity of polyubiquitin chain engagement by the AAA+ ATPase Cdc48.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Induced degradation of Ufd1 reveals regulation of cohesin by the VCP/p97Life science alliance · 2026Article
- ATP-independent unfolding of ubiquitin by Ufd1 initiates Cdc48/p97-mediated substrate processing.Nature structural & molecular biology · 2026Article
- 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
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.Research square · 2026Article
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.bioRxiv : the preprint server for biology · 2026Article
- Direct observation of ATP-driven ubiquitin chain handling by Cdc48.Nature communications · 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 OsRqc1-OsVms1 module regulates the temperature threshold in thermo-sensitive genic male-sterile rice lines.Science China. Life sciences · 2025Article
- NUB1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome.Nature structural & molecular biology · 2025Article
- Mechanism of nascent chain removal by the ribosome-associated quality control complex.Nature communications · 2025Article
- Recent progress and future challenges in structure-based protein-protein interaction prediction.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The ribosome-associated quality control factor TCF25 imposes K48 specificity on Listerin-mediated ubiquitination of nascent chains by binding and specifically orienting the acceptor ubiquitin.Genes & development · 2025Article
- UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains.Molecular cell · 2025Article
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.Nature structural & molecular biology · 2024Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The AAA+ ATPase Cdc48 utilizes the cofactor Ufd1/Npl4 to bind and thread polyubiquitinated substrates for their extraction from complexes or membranes and often for subsequent proteasomal degradation. Previous studies indicated that Cdc48 engages polyubiquitin chains through the Npl4-mediated unfolding of an initiator ubiquitin; yet, the underlying principles remain largely unknown. Using FRET-based assays, we revealed the mechanisms and kinetics of ubiquitin unfolding, insertion into the ATPase, and unfolding of the ubiquitin-attached substrate. We found that Cdc48 uses Ufd1's UT3 domain to bind a K48-linked ubiquitin on the initiator's proximal side of the chain, thereby directing the initiator toward rapid unfolding by Npl4 and engagement by Cdc48. Ubiquitins on the initiator's distal side increase substrate affinity and facilitate unfolding but impede substrate release from Cdc48-Ufd1/Npl4 in the absence of additional cofactors. Our findings explain how Cdc48-UN efficiently processes substrates with K48-linked chains of 4-6 ubiquitins, which represent most cellular polyubiquitinated proteins.
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