ArticlePloS one2012
Usp14 deficiency increases tau phosphorylation without altering tau degradation or causing tau-dependent deficits.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Novel Small-Molecule Analogues of IU1 Ameliorate Amyloid-β Mediated Toxicity in Alzheimer's Disease Cell and Worm Models.International journal of molecular sciences · 2026Article
- Deubiquitinating enzymes at the crossroads of blood-brain barrier integrity and neurodegeneration: mechanistic insights, therapeutic targeting and future directions.Tissue barriers · 2026Review
- Benchmarking In-Cell Proteomics for Profiling Neuroblastoma Cell Differentiation and the Ubiquitin-Proteasome System.Journal of proteome research · 2025Article
- Review
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- Usp14 deficiency removes α-synuclein by regulating S100A8/A9 in Parkinson's disease.Cellular and molecular life sciences : CMLS · 2024Article
- USP14 promotes pyroptosis of human annulus fibrosus cells derived from patients with intervertebral disc degeneration through deubiquitination of NLRP3.Acta biochimica et biophysica Sinica · 2022Article
- Article
- Examination of genetic and pharmacological tools to study the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14 in the nervous system.Journal of neurochemistry · 2021Article
- Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective.Cell death and differentiation · 2021Review
- Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells.PloS one · 2019Article
- Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents.Cancer metastasis reviews · 2017Review
- Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation.Molecular and cellular biochemistry · 2017Article
- Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases?F1000Research · 2016Article
- Inhibition of 19S proteasome-associated deubiquitinases by metal-containing compounds.Oncoscience · 2015Review
- An optimal ubiquitin-proteasome pathway in the nervous system: the role of deubiquitinating enzymes.Frontiers in molecular neuroscience · 2014Review
- Protein degradation and protein synthesis in long-term memory formation.Frontiers in molecular neuroscience · 2014Review
- Protein phosphorylation in neurodegeneration: friend or foe?Frontiers in molecular neuroscience · 2014Review
- Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14).PloS one · 2013Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Regulated protein degradation by the proteasome plays an essential role in the enhancement and suppression of signaling pathways in the nervous system. Proteasome-associated factors are pivotal in ensuring appropriate protein degradation, and we have previously demonstrated that alterations in one of these factors, the proteasomal deubiquitinating enzyme ubiquitin-specific protease 14 (Usp14), can lead to proteasome dysfunction and neurological disease. Recent studies in cell culture have shown that Usp14 can also stabilize the expression of over-expressed, disease-associated proteins such as tau and ataxin-3. Using Usp14-deficient ax(J) mice, we investigated if loss of Usp14 results in decreased levels of endogenous tau and ataxin-3 in the nervous system of mice. Although loss of Usp14 did not alter the overall neuronal levels of tau and ataxin-3, we found increased levels of phosphorylated tau that correlated with the onset of axonal varicosities in the Usp14-deficient mice. These changes in tau phosphorylation were accompanied by increased levels of activated phospho-Akt, phosphorylated MAPKs, and inactivated phospho-GSK3β. However, genetic ablation of tau did not alter any of the neurological deficits in the Usp14-deficient mice, demonstrating that increased levels of phosphorylated tau do not necessarily lead to neurological disease. Due to the widespread activation of intracellular signaling pathways induced by the loss of Usp14, a better understanding of the cellular pathways regulated by the proteasome is required before effective proteasomal-based therapies can be used to treat chronic neurological diseases.
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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.