ArticleMolecular membrane biology2015
The multidrug resistance pump ABCB1 is a substrate for the ubiquitin ligase NEDD4-1.
Article in Molecular membrane biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
- UPS-mediated P-glycoprotein regulation in Alzheimer's disease: pharmacological implications for the amyloid pathology.Molecular biology reports · 2026Review
- TMEM207-mediated the impairment of skin regeneration through YAP sequestration in an allergic contact dermatitis model.Biochemistry and biophysics reports · 2026Article
- Indole-3-Acetic Acid and Skatole Exert Opposing Effects on MDR1 Proteostasis in Human Colonic Epithelial Cells: A Molecular Basis for the Gut Microbial Metabolic Switch.Journal of xenobiotics · 2026Article
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.Fluids and barriers of the CNS · 2025Article
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.Frontiers in aging neuroscience · 2024Review
- Proteasome inhibition protects blood-brain barrier P-glycoprotein and lowers Aβ brain levels in an Alzheimer's disease model.Fluids and barriers of the CNS · 2023Article
- ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.Pharmacological reviews · 2023Review
- Identification and Empiric Evaluation of New Inhibitors of the Multidrug Transporter P-Glycoprotein (ABCB1).International journal of molecular sciences · 2023Article
- Regulation of P-Glycoprotein in the Brain.International journal of molecular sciences · 2022Review
- Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta.Pharmaceutics · 2022Review
- Review
- The Ubiquitin E3 Ligase Nedd4 Regulates the Expression and Amyloid-β Peptide Export Activity of P-Glycoprotein.International journal of molecular sciences · 2022Article
- Rutaecarpine Increases Anticancer Drug Sensitivity in Drug-Resistant Cells through MARCH8-Dependent ABCB1 Degradation.Biomedicines · 2021Article
- ABCB1 Does Not Require the Side-Chain Hydrogen-Bond Donors GlnInternational journal of molecular sciences · 2021Article
- Protecting P-glycoprotein at the blood-brain barrier from degradation in an Alzheimer's disease mouse model.Fluids and barriers of the CNS · 2021Article
- A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer's Pathogenesis-And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder.International journal of molecular sciences · 2021Review
- The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- David S. Miller: Scientist, Mentor, Friend-a tribute and thank you.Fluids and barriers of the CNS · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The ATP Binding Cassette transporter ABCB1 can export the neurotoxic peptide β-amyloid from endothelial cells that line the blood-brain barrier (BBB). This has the potential to lower cerebral levels of β-amyloid, but ABCB1 expression in the BBB appears to be progressively reduced in patients with Alzheimer's disease. The surface density of many membrane proteins is regulated by ubiquitination catalyzed by ubiquitin E3 ligases. In brain capillaries of mice challenged with β-amyloid ex vivo, we show that the level of the ubiquitin ligase Nedd4 increases concomitant with reduction in Abcb1. In vitro we show that human ABCB1 is a substrate for human NEDD4-1 ligase. Recombinant ABCB1 was purified from Sf21 insect cells and incubated with recombinant NEDD4-1 purified from Escherichia coli. The treated ABCB1 had reduced mobility on SDS-PAGE, and mass spectrometry identified eight lysine residues, K271, K272, K575, K685, K877, K885, K887 and K1062 that were ubiquitinated by NEDD4-1. Molecular modelling showed that all of the residues are exposed on the surface of the intracellular domains of ABCB1. K877, K885 and K887 in particular, are located in the intracellular loop of transmembrane helix 10 (TMH10) in close proximity, in the tertiary fold, to a putative NEDD4-1 binding site in the intracellular helix extending from TMH12 (PxY motif, residues 996-998). Transient expression of NEDD4-1 in HEK293 Flp-In cells stably expressing ABCB1 was shown to reduce the surface density of the transporter. Together, the data identify this ubiquitin ligase as a potential target for intervention in the pathophysiology of Alzheimer's disease.
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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.