ArticleMolecular cell2024
Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- 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
- Assessing the suitability of deubiquitylases as substrates for targeted protein degradation.Cell chemical biology · 2026Article
- Article
- The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation.Scientific reports · 2026Article
- The accessory adapters FAF1, FAF2, and UBXN7 accelerate proteasomal degradation by increasing prior p97-mediated substrate unfolding.Science advances · 2026Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Structural variations in evolutionary novel genomic regions: new insights into neurodevelopmental disorders by long-read DNA Sequencing.Molecular medicine (Cambridge, Mass.) · 2026Article
- The many faces of p97/Cdc48 in mitochondrial homeostasis.Essays in biochemistry · 2025Review
- Structure of the TXNL1-bound proteasome.Nature structural & molecular biology · 2025Article
- The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation.bioRxiv : the preprint server for biology · 2025Article
- Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.The Journal of cell biology · 2025Article
- Exploring Yeast's Energy Dynamics: The General Stress Response Lowers Maintenance Energy Requirement.Microbial biotechnology · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Elucidation of the late steps in the glycan-dependent ERAD of soluble misfolded glycoproteins.The Plant journal : for cell and molecular biology · 2025Article
- Integrative Omics reveals changes in the cellular landscape of peroxisome-deficientMicrobial cell (Graz, Austria) · 2025Article
- Comparative Proteome-Wide Abundance Profiling of Yeast Strains Deleted for Cdc48 Adaptors.Proteomes · 2024Article
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5 authors at 2 institutions in 1 country.
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Abstract
Most eukaryotic proteins are degraded by the 26S proteasome after modification with a polyubiquitin chain. Substrates lacking unstructured segments cannot be degraded directly and require prior unfolding by the Cdc48 ATPase (p97 or VCP in mammals) in complex with its ubiquitin-binding partner Ufd1-Npl4 (UN). Here, we use purified yeast components to reconstitute Cdc48-dependent degradation of well-folded model substrates by the proteasome. We show that a minimal system consists of the 26S proteasome, the Cdc48-UN ATPase complex, the proteasome cofactor Rad23, and the Cdc48 cofactors Ubx5 and Shp1. Rad23 and Ubx5 stimulate polyubiquitin binding to the 26S proteasome and the Cdc48-UN complex, respectively, allowing these machines to compete for substrates before and after their unfolding. Shp1 stimulates protein unfolding by the Cdc48-UN complex rather than substrate recruitment. Experiments in yeast cells confirm that many proteins undergo bidirectional substrate shuttling between the 26S proteasome and Cdc48 ATPase before being degraded.
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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.