ArticleJournal of cell science2014
The requirement for Cdc48/p97 in nuclear protein quality control degradation depends on the substrate and correlates with substrate insolubility.
Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions.Nucleic acids research · 2025Article
- VCP activator reverses nuclear proteostasis defects and enhances TDP-43 aggregate clearance in multisystem proteinopathy models.The Journal of clinical investigation · 2024Article
- Proteomics analysis reveals the differential impact of the p97 inhibitor CB-5083 on protein levels in various cellular compartments of the HL-60 cell line.microPublication biology · 2024Article
- Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns.The EMBO journal · 2023Article
- HSP70-binding motifs function as protein quality control degrons.Cellular and molecular life sciences : CMLS · 2023Article
- Reversible protein assemblies in the proteostasis network in health and disease.Frontiers in molecular biosciences · 2023Review
- Quality control of cytoplasmic proteins inside the nucleus.Computational and structural biotechnology journal · 2022Review
- Ubiquitin Ligase Redundancy and Nuclear-Cytoplasmic Localization in Yeast Protein Quality Control.Biomolecules · 2021Review
- The San1 Ubiquitin Ligase Avidly Recognizes Misfolded Proteins through Multiple Substrate Binding Sites.Biomolecules · 2021Article
- Inner-nuclear-membrane-associated degradation employs Dfm1-independent retrotranslocation and alleviates misfolded transmembrane-protein toxicity.Molecular biology of the cell · 2021Article
- Emerging role of VCP/p97 in cardiovascular diseases: novel insights and therapeutic opportunities.Biochemical Society transactions · 2021Review
- Proteotoxicity: A Fatal Consequence of Environmental Pollutants-Induced Impairments in Protein Clearance Machinery.Journal of personalized medicine · 2021Review
- Nuclear Ubiquitin-Proteasome Pathways in Proteostasis Maintenance.Biomolecules · 2021Review
- Direct involvement of Hsp70 ATP hydrolysis in Ubr1-dependent quality control.Molecular biology of the cell · 2020Article
- Recovery of motor function of chronic spinal cord injury by extracellular pyruvate kinase isoform M2 and the underlying mechanism.Scientific reports · 2020Article
- Article
- The extent of Ssa1/Ssa2 Hsp70 chaperone involvement in nuclear protein quality control degradation varies with the substrate.Molecular biology of the cell · 2020Article
- Patrolling the nucleus: inner nuclear membrane-associated degradation.Current genetics · 2019Review
- Proteasomes and Several Aspects of Their Heterogeneity Relevant to Cancer.Frontiers in oncology · 2019Review
- Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation Pathways: a Link to Neurodegeneration.Molecular neurobiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cdc48, known as p97 or valosin-containing protein (VCP) in mammals, is an abundant AAA-ATPase that is essential for many ubiquitin-dependent processes. One well-documented role for Cdc48 is in facilitating the delivery of ubiquitylated misfolded endoplasmic reticulum proteins to the proteasome for degradation. By contrast, the role for Cdc48 in misfolded protein degradation in the nucleus is unknown. In the budding yeast Saccharomyces cerevisiae, degradation of misfolded proteins in the nucleus is primarily mediated by the nuclear-localized ubiquitin-protein ligase San1, which ubiquitylates misfolded nuclear proteins for proteasomal degradation. Here, we find that, although Cdc48 is involved in the degradation of some San1 substrates, it is not universally required. The difference in the requirement for Cdc48 correlates with the insolubility of the San1 substrate. The more insoluble the substrate, the more its degradation requires Cdc48. Expression of Cdc48-dependent San1 substrates in mutant cdc48 cells results in increased substrate insolubility, larger inclusion formation and reduced cell viability. Substrate ubiquitylation is increased in mutant cdc48 cells, suggesting that Cdc48 functions downstream of San1. Taken together, we propose that Cdc48 acts, in part, to maintain the solubility or reverse the aggregation of insoluble misfolded proteins prior to their proteasomal degradation.
Indexed as
Identifiers
What OpenQuestion holds
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.