ArticleBiochimica et biophysica acta2015
Revealing the fate of cell surface human P-glycoprotein (ABCB1): The lysosomal degradation pathway.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Breaking the Efflux Barrier: P-Glycoprotein and Emerging Strategies to Overcome Multidrug Resistance in Cancer.Cancers · 2026Review
- Lysosomal Drug Sequestration Mediated by ABC Transporters and Drug Resistance.Pharmaceutics · 2025Article
- LightSpot Fluorescent Conjugates as Highly Efficient Tools for Lysosomal P-gp Quantification in Olaparib-Treated Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Sucralose Promotes Benzo(a)Pyrene-Induced Renal Toxicity in Mice by Regulating P-glycoprotein.Antioxidants (Basel, Switzerland) · 2025Article
- Ferric Ammonium Citrate Reduces Claudin-5 Abundance and Function in Primary Mouse Brain Endothelial Cells.Pharmaceutical research · 2025Article
- Molecular Phenotypes Segregate Missense Mutations in SLC13A5 Epilepsy.Journal of molecular biology · 2024Article
- Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- The β Isoform of Human ATP-Binding Cassette B5 Transporter, ABCB5β, Localizes to the Endoplasmic Reticulum.International journal of molecular sciences · 2023Article
- Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications.International journal of molecular sciences · 2023Article
- SORL1 stabilizes ABCB1 to promote cisplatin resistance in ovarian cancer.Functional & integrative genomics · 2023Article
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- The Ubiquitin E3 Ligase Nedd4 Regulates the Expression and Amyloid-β Peptide Export Activity of P-Glycoprotein.International journal of molecular sciences · 2022Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- Teaching an old dog new tricks: reactivated developmental signaling pathways regulate ABCB1 and chemoresistance in cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?Pharmaceutics · 2020Review
- Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy.The AAPS journal · 2020Article
- The Effects of TiOInternational journal of molecular sciences · 2020Article
- Influence of lysosomal sequestration on multidrug resistance in cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Regulation of ABCB1 activity by microRNA-200c and microRNA-203a in breast cancer cells: the quest for microRNAs' involvement in cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
P-glycoprotein (P-gp) transports a variety of chemically dissimilar amphipathic compounds including anticancer drugs. Although mechanisms of P-gp drug transport are widely studied, the pathways involving its internalization are poorly understood. The present study is aimed at elucidating the pathways involved in degradation of cell surface P-gp. The fate of P-gp at the cell surface was determined by biotinylating cell surface proteins followed by flow cytometry and Western blotting. Our data shows that the half-life of endogenously expressed P-gp is 26.7±1.1 h in human colorectal cancer HCT-15 cells. Treatment of cells with Bafilomycin A1 (BafA1) a vacuolar H+ ATPase inhibitor increased the half-life of P-gp at the cell surface to 36.1±0.5 h. Interestingly, treatment with the proteasomal inhibitors MG132, MG115 or lactacystin alone did not alter the half-life of the protein. When cells were treated with both lysosomal and proteasomal inhibitors (BafA1 and MG132), the half-life was further prolonged to 39-50 h. Functional assays done with rhodamine 123 or calcein-AM, fluorescent substrates of P-gp, indicated that the transport function of P-gp was not affected by either biotinylation or treatment with BafA1 or proteasomal inhibitors. Immunofluorescence studies done with the antibody against lysosomal marker LAMP1 and the P-gp-specific antibody UIC2 in permeabilized cells indicated that intracellular P-gp is primarily localized in the lysosomal compartment. Our results suggest that the lysosomal degradation system could be targeted to increase the sensitivity of P-gp- expressing cancer cells towards chemotherapeutic drugs.
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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.