ArticleThe Journal of biological chemistry2014
The ubiquitin C-terminal hydrolase L1 (UCH-L1) C terminus plays a key role in protein stability, but its farnesylation is not required for membrane association in primary neurons.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Early Retinal UCHL1 Dysregulation Coupled With Synaptic Loss Reflects Alzheimer's Disease Severity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ketogenic diet regulates Uch-L1(C) to improve cerebral energy metabolism and cognitive function in Alzheimer's disease mice.European journal of histochemistry : EJH · 2026Article
- UCH-L1 in Alzheimer's Disease: A Crucial Player in Dementia-Associated Mechanisms.International journal of molecular sciences · 2025Review
- From Acute Injury to Chronic Neurodegeneration: Molecular Mechanisms Linking Secondary Brain Injury to Long-Term Pathology.International journal of molecular sciences · 2025Review
- Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers.Annals of neurology · 2025Observational
- Abolishing UCHL1's hydrolase activity exacerbates ischemia-induced axonal injury and functional deficits in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Data-independent acquisition proteomics of cerebrospinal fluid implicates endoplasmic reticulum and inflammatory mechanisms in amyotrophic lateral sclerosis.Journal of neurochemistry · 2024Article
- Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Altered ubiquitin signaling induces Alzheimer's disease-like hallmarks in a three-dimensional human neural cell culture model.Nature communications · 2023Article
- Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury.Ageing research reviews · 2023Review
- Review
- Role of the deubiquitinating enzyme UCH-L1 in mitochondrial function.Frontiers in cellular neuroscience · 2023Article
- Article
- Structural basis for specific inhibition of the deubiquitinase UCHL1.Nature communications · 2022Article
- Tripartite Separation of Glomerular Cell Types and Proteomes from Reporter-Free Mice.Journal of the American Society of Nephrology : JASN · 2021Article
- Optimization and Anti-Cancer Properties of Fluoromethylketones as Covalent Inhibitors for Ubiquitin C-Terminal Hydrolase L1.Molecules (Basel, Switzerland) · 2021Article
- Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion.Journal of neurology · 2020Article
- Molecular evolutionary and structural analysis of human UCHL1 gene demonstrates the relevant role of intragenic epistasis in Parkinson's disease and other neurological disorders.BMC evolutionary biology · 2020Article
- The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases.International journal of molecular sciences · 2020Review
- Regulation of Deubiquitinating Enzymes by Post-Translational Modifications.International journal of molecular sciences · 2020Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons. A possible role for UCH-L1 in neurodegeneration has been highlighted because of its presence in Lewy bodies associated with Parkinson disease and neurofibrillary tangles observed in Alzheimer disease. UCH-L1 exists in two forms in neurons, a soluble cytoplasmic form (UCH-L1(C)) and a membrane-associated form (UCH-L1(M)). Alzheimer brains show reduced levels of soluble UCH-L1(C) correlating with the formation of UCH-L1-immunoreactive tau tangles, whereas UCH-L1(M) has been implicated in α-synuclein dysfunction. Given these reports of divergent roles, we investigated the properties of UCH-L1 membrane association. Surprisingly, our results indicate that UCH-L1 does not partition to the membrane in the cultured cell lines we tested. Furthermore, in primary cultured neurons, a proportion of UCH-L1(M) does partition to the membrane, but, contrary to a previous report, this does not require farnesylation. Deletion of the four C-terminal residues caused the loss of protein solubility, abrogation of substrate binding, increased cell death, and an abnormal intracellular distribution, consistent with protein dysfunction and aggregation. These data indicate that UCH-L1 is differently processed in neurons compared with clonal cell lines and that farnesylation does not account for the membrane association in neurons.
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