ArticleThe Journal of biological chemistry2010
Valosin-containing protein (VCP) in novel feedback machinery between abnormal protein accumulation and transcriptional suppression.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- ASPL-driven subunit exchange remodels VCP/p97 hexamers and is impaired by a multisystem proteinopathy mutation.bioRxiv : the preprint server for biology · 2026Article
- The VCPKMT-VCP-HDAC1 axis inhibits colorectal cancer by conferring sensitivity to ferroptosis.Cancer cell international · 2025Article
- VCP activator reverses nuclear proteostasis defects and enhances TDP-43 aggregate clearance in multisystem proteinopathy models.The Journal of clinical investigation · 2024Article
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis.Scientific reports · 2020Article
- The Interplay of Cofactor Interactions and Post-translational Modifications in the Regulation of the AAA+ ATPase p97.Frontiers in molecular biosciences · 2017Review
- Linker histone H1 and protein-protein interactions.Biochimica et biophysica acta · 2016Review
- Age-dependent Effects of 17β-estradiol on the dynamics of estrogen receptor β (ERβ) protein-protein interactions in the ventral hippocampus.Molecular & cellular proteomics : MCP · 2014Article
- Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.PloS one · 2014Article
- Regulation of molecular chaperones through post-translational modifications: decrypting the chaperone code.Biochimica et biophysica acta · 2013Review
- Mdm20 stimulates polyQ aggregation via inhibiting autophagy through Akt-Ser473 phosphorylation.PloS one · 2013Article
- A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.Nature communications · 2013Article
- VCP Is an integral component of a novel feedback mechanism that controls intracellular localization of catalase and H2O2 Levels.PloS one · 2013Article
- A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.PLoS genetics · 2013Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal protein accumulation is often observed in human neurodegenerative disorders such as polyglutamine diseases and Parkinson disease. Genetic and biochemical analyses indicate that valosin-containing protein (VCP) is a crucial molecule in the pathogenesis of human neurodegenerative disorders. We report here that VCP was specifically modified in neuronal cells with abnormal protein accumulation; this modification caused the translocation of VCP into the nucleus. Modification-mimic forms of VCP induced transcriptional suppression with deacetylation of core histones, leading to cell atrophy and the decrease of de novo protein synthesis. Preventing VCP nuclear translocation in polyglutamine-expressing neuronal cells and Drosophila eyes mitigated neurite retraction and eye degenerations, respectively, concomitant with the recovery of core histone acetylation. This represents a novel feedback mechanism that regulates abnormal protein levels in the cytoplasm during physiological processes, as well as in pathological conditions such as abnormal protein accumulation in neurodegenerations.
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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.