ArticleThe Journal of biological chemistry2016
Cathepsin Protease Controls Copper and Cisplatin Accumulation via Cleavage of the Ctr1 Metal-binding Ectodomain.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
The trial behind it
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
24 citing papers in PubMed, 54 citations in OpenAlex.
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Copper import via CTR1 supports the β3-Adrenergic thermogenic program.Molecular metabolism · 2026Article
- Copper Import via CTR1 Supports the β3-Adrenergic Thermogenic Program.bioRxiv : the preprint server for biology · 2026Article
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives.Frontiers in pharmacology · 2025Review
- Copper in Gynecological Diseases.International journal of molecular sciences · 2023Review
- Revisiting the Anti-Cancer Toxicity of Clinically Approved Platinating Derivatives.International journal of molecular sciences · 2022Review
- The copper transporter CTR1 and cisplatin accumulation at the single-cell level by LA-ICP-TOFMS.Frontiers in molecular biosciences · 2022Article
- Oral Elesclomol Treatment Alleviates Copper Deficiency in Animal Models.Frontiers in cell and developmental biology · 2022Article
- Crossroads between membrane trafficking machinery and copper homeostasis in the nerve system.Open biology · 2021Review
- Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.Seminars in cancer biology · 2021Review
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Copper metabolism as a unique vulnerability in cancer.Biochimica et biophysica acta. Molecular cell research · 2021Review
- The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents.Frontiers in pharmacology · 2020Review
- Review
- New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment.International journal of molecular sciences · 2019Review
- X-ray structures of the high-affinity copper transporter Ctr1.Nature communications · 2019Article
- Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale.International journal of chronic obstructive pulmonary disease · 2019Article
- Reconstitution of a thermophilic CuThe Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Copper is an essential metal ion for embryonic development, iron acquisition, cardiac function, neuropeptide biogenesis, and other critical physiological processes. Ctr1 is a high affinity Cu(+) transporter on the plasma membrane and endosomes that exists as a full-length protein and a truncated form of Ctr1 lacking the methionine- and histidine-rich metal-binding ectodomain, and it exhibits reduced Cu(+) transport activity. Here, we identify the cathepsin L/B endolysosomal proteases functioning in a direct and rate-limiting step in the Ctr1 ectodomain cleavage. Cells and mice lacking cathepsin L accumulate full-length Ctr1 and hyper-accumulate copper. As Ctr1 also transports the chemotherapeutic drug cisplatin via direct binding to the ectodomain, we demonstrate that the combination of cisplatin with a cathepsin L/B inhibitor enhances cisplatin uptake and cell killing. These studies identify a new processing event and the key protease that cleaves the Ctr1 metal-binding ectodomain, which functions to regulate cellular Cu(+) and cisplatin acquisition.
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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.