ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.Journal of translational medicine · 2024Review
- Insights into the Role of Histone Methylation in Brain Aging and Potential Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities.Frontiers in cell and developmental biology · 2023Review
- Proteasome Complexes and Their Heterogeneity in Colorectal, Breast and Pancreatic Cancers.Journal of Cancer · 2021Article
- Cell-Clearing Systems Bridging Repeat Expansion Proteotoxicity and Neuromuscular Junction Alterations in ALS and SBMA.International journal of molecular sciences · 2020Review
- Qualitative Assay to Detect Dopamine Release by Ligand Action on Nicotinic Acetylcholine Receptors.Toxins · 2019Article
- Computational analysis of single-cell transcriptomics data elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo.Scientific reports · 2019Article
- UBXN2A enhances CHIP-mediated proteasomal degradation of oncoprotein mortalin-2 in cancer cells.Molecular oncology · 2018Article
- Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: an update.British journal of pharmacology · 2018Review
- Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2017Article
- UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer.International journal of molecular sciences · 2016Review
- Valosin-containing protein (VCP)-Adaptor Interactions are Exceptionally Dynamic and Subject to Differential Modulation by a VCP Inhibitor.Molecular & cellular proteomics : MCP · 2016Article
- Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy.Cell stress & chaperones · 2016Article
- Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use.Genes, brain, and behavior · 2016Review
- UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP.Biochemical pharmacology · 2015Article
- A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2.Oncotarget · 2015Article
- Nucleocytoplasmic Translocation of UBXN2A Is Required for Apoptosis during DNA Damage Stresses in Colon Cancer Cells.Journal of Cancer · 2015Article
- Nicotine withdrawal.Current topics in behavioral neurosciences · 2015Review
- Ubiquitin-like (UBX)-domain-containing protein, UBXN2A, promotes cell death by interfering with the p53-Mortalin interactions in colon cancer cells.Cell death & disease · 2014Article
- Chemical crosslinkers enhance detection of receptor interactomes.Frontiers in pharmacology · 2014Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Adaptor proteins are likely to modulate spatially and temporally the trafficking of a number of membrane proteins, including neuronal nicotinic acetylcholine receptors (nAChRs). A yeast two-hybrid screen identified a novel UBX-containing protein, UBXD4, as one of the cytosolic proteins that interact directly with the alpha3 and alpha4 nAChR subunits. The function of UBX-containing proteins is largely unknown. Immunoprecipitation and confocal microscopy confirmed the interaction of UBXD4 with alpha3-containing nAChRs (alpha3* nAChRs) expressed in HEK293 cells, PC12 cells, and rat cortical neurons. Overexpression of UBXD4 in differentiated PC12 cells (dPC12) increased nAChR cell surface expression, especially that of the alpha3beta2 subtype. These findings were corroborated by electrophysiology, immunofluorescent staining, and biotinylation of surface receptors. Silencing of UBXD4 led to a significant reduction of alpha3* nAChRs in rat cortical neurons and dPC12 cells. Biochemical and immunofluorescence studies of endogenous UBXD4 showed that the protein is located in both the ER and cis-Golgi compartments. Our investigations also showed that the alpha3 subunit is ubiquitinated and that UBXD4 can interfere with its ubiquitination and consequent degradation by the proteasome. Our data suggest that UBXD4 modulates the distribution of alpha3* nAChRs between specialized intracellular compartments and the plasma membrane. This effect is achieved by controlling the stability of the alpha3 subunit and, consequently, the number of receptors at the cell surface.
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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.