ArticleThe Journal of cell biology2000
Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Meta-analysis of Ubiquilin1 gene polymorphism and Alzheimer's disease risk.Medical science monitor : international medical journal of experimental and clinical research · 2014Pooled it
- Ubiquilin 1 Inhibits intracellular proliferation of Salmonella enterica serovar Typhimurium through Xenophagy.Genes & genomics · 2026Article
- STI1 domains coordinate partitioning of UBQLN2 into stress-induced condensates.bioRxiv : the preprint server for biology · 2026Article
- UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.Biochemical Society transactions · 2025Review
- Downregulation of Lnc-ABCA12-3 modulates UBQLN1 expression and protein homeostasis pathways in amyotrophic lateral sclerosis.Scientific reports · 2024Article
- Short disordered termini and proline-rich domain are major regulators of UBQLN1/2/4 phase separation.Biophysical journal · 2024Article
- Towards a molecular understanding of the overlapping and distinct roles of UBQLN1 and UBQLN2 in lung cancer progression and metastasis.Neoplasia (New York, N.Y.) · 2022Article
- Association of the Protein-Quality-Control Protein Ubiquilin-1 With Alzheimer's Disease BothFrontiers in neuroscience · 2022Article
- Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling.Oncology reports · 2021Article
- ALS-linked mutations impair UBQLN2 stress-induced biomolecular condensate assembly in cells.Journal of neurochemistry · 2021Article
- ALS/FTD mutations in UBQLN2 are linked to mitochondrial dysfunction through loss-of-function in mitochondrial protein import.Human molecular genetics · 2021Article
- Shared and divergent phase separation and aggregation properties of brain-expressed ubiquilins.Scientific reports · 2021Article
- Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells.Journal of cellular biochemistry · 2021Article
- Proteasome Biology: Chemistry and Bioengineering Insights.Polymers · 2020Review
- Ubiquitin-Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Review
- Overexpression of UBQLN1 reduces neuropathology in the P497S UBQLN2 mouse model of ALS/FTD.Acta neuropathologica communications · 2020Article
- Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery.The Biochemical journal · 2020Review
- ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The specificity of ubiquitin binding to ubiquilin-1 is regulated by sequences besides its UBA domain.Biochimica et biophysica acta. General subjects · 2019Article
- Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration.International journal of molecular sciences · 2019Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the highly homologous presenilin genes encoding presenilin-1 and presenilin-2 (PS1 and PS2) are linked to early-onset Alzheimer's disease (AD). However, apart from a role in early development, neither the normal function of the presenilins nor the mechanisms by which mutant proteins cause AD are well understood. We describe here the properties of a novel human interactor of the presenilins named ubiquilin. Yeast two-hybrid (Y2H) interaction, glutathione S-transferase pull-down experiments, and colocalization of the proteins expressed in vivo, together with coimmunoprecipitation and cell fractionation studies, provide compelling evidence that ubiquilin interacts with both PS1 and PS2. Ubiquilin is noteworthy since it contains multiple ubiquitin-related domains typically thought to be involved in targeting proteins for degradation. However, we show that ubiquilin promotes presenilin protein accumulation. Pulse-labeling experiments indicate that ubiquilin facilitates increased presenilin synthesis without substantially changing presenilin protein half-life. Immunohistochemistry of human brain tissue with ubiquilin-specific antibodies revealed prominent staining of neurons. Moreover, the anti-ubiquilin antibodies robustly stained neurofibrillary tangles and Lewy bodies in AD and Parkinson's disease affected brains, respectively. Our results indicate that ubiquilin may be an important modulator of presenilin protein accumulation and that ubiquilin protein is associated with neuropathological neurofibrillary tangles and Lewy body inclusions in diseased brain.
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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.