ArticleCell2016
UBQLN2 Mediates Autophagy-Independent Protein Aggregate Clearance by the Proteasome.
Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis that pooled it.
What it found
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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
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 305 citations in OpenAlex.
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- TBK1 overexpression reduces neuronal loss in the P497S UBQLN2 mouse model of ALS/FTD.Neurobiology of disease · 2026Article
- ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties.bioRxiv : the preprint server for biology · 2026Article
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Synphilin-1 mitigates autophagy dysfusnction, modulates ubiquitinated protein aggregation, and promotes cell survival during proteotoxic stress.bioRxiv : the preprint server for biology · 2026Article
- Structure-function relationship of alpha-synuclein fibrillar polymorphs derived from distinct synucleinopathies.Molecular systems biology · 2026Article
- JAK1/2 inhibitor ruxolitinib reduces aggregates in cardiac proteinopathy.EMBO molecular medicine · 2026Article
- STI1 domains coordinate partitioning of UBQLN2 into stress-induced condensates.bioRxiv : the preprint server for biology · 2026Article
- The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study and Literature Review.Neurology. Genetics · 2026Article
- UBQLN2 links proteotoxicity with lipid metabolism in neurodegeneration.Nature neuroscience · 2026Article
- ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences.The EMBO journal · 2026Article
- Rad23b exacerbates pathological aggregates through disrupting proteasome functions in Spinocerebellar ataxia type 3.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Identification of regulatory candidate genes for Lentinula edodes pileus development based on transcriptome analysis.G3 (Bethesda, Md.) · 2026Article
- PML targets and resolves structured protein inclusions to mitigate neurodegeneration.Nature cell biology · 2026Article
- Peritumoral edema in meningiomas: a review of influencing factors, mechanisms, and management.Frontiers in oncology · 2026Review
- UBQLN2 is necessary for UBE3A-mediated proteasomal degradation of the domesticated retroelement PEG10.Journal of cell science · 2025Article
- Ubiquilin-2 liquid droplets catalyze α-synuclein fibril formation.The EMBO journal · 2025Article
- A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy.Nature cell biology · 2025Article
- UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.Biochemical Society transactions · 2025Review
- Episodic transport of protein aggregates achieves a positive size selectivity in aggresome formation.Nature communications · 2025Article
125 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
Clearance of misfolded and aggregated proteins is central to cell survival. Here, we describe a new pathway for maintaining protein homeostasis mediated by the proteasome shuttle factor UBQLN2. The 26S proteasome degrades polyubiquitylated substrates by recognizing them through stoichiometrically bound ubiquitin receptors, but substrates are also delivered by reversibly bound shuttles. We aimed to determine why these parallel delivery mechanisms exist and found that UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act. Finally, we found that mutations in UBQLN2, which lead to neurodegeneration in humans, are defective in chaperone binding, impair aggregate clearance, and cause cognitive deficits in mice.
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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.