ArticleNature communications2017
An unexpected protein interaction promotes drug resistance in leukemia.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Protein Kinase A and assembly of an ABCC4 protein network.Nature communications · 2025Article
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- MPP1 Determines the Mobility of Flotillins and Controls the Confinement of Raft-Associated Molecules.Cells · 2022Article
- An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.Clinical and translational medicine · 2021Article
- Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.Vox sanguinis · 2021Review
- Not Just Another Scaffolding Protein Family: The Multifaceted MPPs.Molecules (Basel, Switzerland) · 2020Review
- Structural basis for substrate recognition and chemical inhibition of oncogenic MAGE ubiquitin ligases.Nature communications · 2020Article
- An ABC Transporter Drives Medulloblastoma Pathogenesis by Regulating Sonic Hedgehog Signaling.Cancer research · 2020Article
- Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5.Journal of medicinal chemistry · 2020Article
- Article
- Genome-wide identification of FHL1 as a powerful prognostic candidate and potential therapeutic target in acute myeloid leukaemia.EBioMedicine · 2020Article
- A high-throughput screening identifies histone deacetylase inhibitors as therapeutic agents against medulloblastoma.Experimental hematology & oncology · 2019Article
- Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions as Potential Mechanisms of Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
The overall survival of patients with acute myeloid leukemia (AML) is poor and identification of new disease-related therapeutic targets remains a major goal for this disease. Here we show that expression of MPP1, a PDZ-domain-containing protein, highly correlated with ABCC4 in AML, is associated with worse overall survival in AML. Murine hematopoietic progenitor cells overexpressing MPP1 acquired the ability to serially replate in methylcellulose culture, a property crucially dependent upon ABCC4. The highly conserved PDZ-binding motif of ABCC4 is required for ABCC4 and MPP1 to form a protein complex, which increased ABCC4 membrane localization and retention, to enhance drug resistance. Specific disruption of this protein complex, either genetically or chemically, removed ABCC4 from the plasma membrane, increased drug sensitivity, and abrogated MPP1-dependent hematopoietic progenitor cell replating in methylcellulose. High-throughput screening identified Antimycin A as a small molecule that disrupted the ABCC4-MPP1 protein complex and reversed drug resistance in AML cell lines and in primary patient AML cells. In all, targeting the ABCC4-MPP1 protein complex can lead to new therapies to improve treatment outcome of AML, a disease where the long-term prognosis is poor.
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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.