ArticleCell reports2020
The Cdc48 Complex Alleviates the Cytotoxicity of Misfolded Proteins by Regulating Ubiquitin Homeostasis.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Regulation of misfolded protein aggregation and degradation by SUMOylation in budding yeast.Molecular biology of the cell · 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
- Comparative Proteome-Wide Abundance Profiling of Yeast Strains Deleted for Cdc48 Adaptors.Proteomes · 2024Article
- Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation.Molecular cell · 2024Article
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Multiple phosphorylation of the Cdc48/p97 cofactor protein Shp1/p47 occurs upon cell stress in budding yeast.Life science alliance · 2023Article
- Article
- Neurodegenerative disease-associated inclusion bodies are cleared by selective autophagy in budding yeast.Autophagy reports · 2023Article
- A Potential Mechanism for Targeting Aggregates With Proteasomes and Disaggregases in Liquid Droplets.Frontiers in aging neuroscience · 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
- Article
- Review
- Mapping the degradation pathway of a disease-linked aspartoacylase variant.PLoS genetics · 2021Article
- Article
- Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The accumulation of misfolded proteins is associated with multiple neurodegenerative disorders, but it remains poorly defined how this accumulation causes cytotoxicity. Here, we demonstrate that the Cdc48/p97 segregase machinery drives the clearance of ubiquitinated model misfolded protein Huntingtin (Htt103QP) and limits its aggregation. Nuclear ubiquitin ligase San1 acts upstream of Cdc48 to ubiquitinate Htt103QP. Unexpectedly, deletion of SAN1 and/or its cytosolic counterpart UBR1 rescues the toxicity associated with Cdc48 deficiency, suggesting that ubiquitin depletion, rather than compromised proteolysis of misfolded proteins, causes the growth defect in cells with Cdc48 deficiency. Indeed, Cdc48 deficiency leads to elevated protein ubiquitination levels and decreased free ubiquitin, which depends on San1/Ubr1. Furthermore, enhancing free ubiquitin levels rescues the toxicity in various Cdc48 pathway mutants and restores normal turnover of a known Cdc48-independent substrate. Our work highlights a previously unappreciated function for Cdc48 in ensuring the regeneration of monoubiquitin that is critical for normal cellular function.
Indexed as
Identifiers
What Socratic 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 Socratic graph.