ReviewFrontiers in molecular biosciences2023
Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine.
Review in Frontiers in molecular biosciences, 2023. 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, 34 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
- Direct observation of ATP-driven ubiquitin chain handling by Cdc48.Nature communications · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.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
- The many faces of p97/Cdc48 in mitochondrial homeostasis.Essays in biochemistry · 2025Review
- Molecular Tweezers Block the Functional Pore of a Protein Machine.Journal of the American Chemical Society · 2025Article
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- PIN1-SUMO2/3 motif suppresses excessive RNF168 chromatin accumulation and ubiquitin signaling to promote IR resistance.Nature communications · 2025Article
- Valosin-containing protein p97 extracts capping protein CP110 from the mother centriole to promote ciliogenesis.Molecular biology of the cell · 2025Article
- Phenotypic screens identify SCAF1 as critical activator of RNAPII elongation and global transcription.Nucleic acids research · 2025Article
- Selenoprotein K at the intersection of cellular pathways.Archives of biochemistry and biophysics · 2025Review
- VCP regulates early tau seed amplification via specific cofactors.Molecular neurodegeneration · 2025Article
- A modular DNA origami nanocompartment for engineering a cell-free, protein unfolding and degradation pathway.Nature nanotechnology · 2024Article
- Does the polyubiquitination pathway operate inside intact chloroplasts to remove proteins?The Plant cell · 2024Article
- Article
- VCP/p97 mediates nuclear targeting of non-ER-imported prion protein to maintain proteostasis.Life science alliance · 2024Article
- VCP regulates early tau seed amplification via specific cofactors.Research square · 2024Article
- VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates.Nature communications · 2024Article
- Analysis of the Conformational Landscape of the N-Domains of the AAA ATPase p97: Disentangling the Continuous Conformational Variability in Partially Symmetrical Complexes.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AAA+ ATPase p97 (also called VCP or Cdc48) is a major protein unfolding machine with hundreds of clients in diverse cellular pathways that are critical for cell homeostasis, proliferation and signaling. In this review, we summarize recent advances in understanding how diverse client proteins are targeted to the p97 machine to facilitate client degradation or to strip clients from binding partners for regulation. We describe an elaborate system that is governed by at least two types of alternative adapters. The Ufd1-Npl4 adapter along with accessory adapters targets ubiquitylated clients in the majority of pathways and uses ubiquitin as a universal unfolding tag. In contrast, the family of SEP-domain adapters such as p37 can target clients directly to p97 in a ubiquitin-independent manner. Despite the different targeting strategies, both pathways converge by inserting the client into the p97 pore to initiate a peptide threading mechanism through the central channel of p97 that drives client protein unfolding, protein extraction from membranes and protein complex disassembly 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.