ArticleMetallomics : integrated biometal science2015
The copper transporter 1 (CTR1) is required to maintain the stability of copper transporter 2 (CTR2).
Article in Metallomics : integrated biometal science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 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
- Genome-wide CRISPR knockout cell screening platform for the disease vector tick speciesbioRxiv : the preprint server for biology · 2026Article
- ADMET Profiling of the Metallodrugs: A Comparative Review of Platinum, Palladium, Gold, Ruthenium, Copper, and Zinc Anticancer Complexes.Bioinorganic chemistry and applications · 2026Review
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- Targeting cuproptosis in liver cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2025Review
- Copper Homeostasis, Emerging Central Players in Cancer Immunotherapy.Journal of cellular and molecular medicine · 2025Review
- Balancing between cuproplasia and copper-dependent cell death: molecular basis and clinical implications of ATOX1 in cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- Nanoparticles induced cuproptosis to enhance antitumor immunotherapy.Journal of nanobiotechnology · 2025Review
- Copper Toxicity in Animals: A Review.Biological trace element research · 2025Review
- Trace Elements in Medicinal Metallomics.Mini reviews in medicinal chemistry · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy.Biomarker research · 2024Review
- Cuproptosis: unveiling a new frontier in cancer biology and therapeutics.Cell communication and signaling : CCS · 2024Review
- Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes.Frontiers in molecular biosciences · 2024Review
- Carnosine, Zinc and Copper: A Menage a Trois in Bone and Cartilage Protection.International journal of molecular sciences · 2023Review
- Copper homeostasis and the ubiquitin proteasome system.Metallomics : integrated biometal science · 2023Review
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- Review
- Copper Metabolism of Newborns Is Adapted to Milk Ceruloplasmin as a Nutritive Source of Copper: Overview of the Current Data.Nutrients · 2018Review
- APTO-253 Is a New Addition to the Repertoire of Drugs that Can Exploit DNA BRCA1/2 Deficiency.Molecular cancer therapeutics · 2018Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Mammalian cells have two influx Cu transporters that form trimers in membranes. CTR1 is the high affinity transporter that resides largely in the plasma membrane, and CTR2 is the low affinity transporter that is primarily associated with vesicular structures inside the cell. The major differences between CTR1 and CTR2 are that CTR1 contains a HIS/MET-rich domain N-terminal of the METS that participate in the first two stacked rings that form the pore, and a longer C-terminal tail that includes a Cu binding HIS-CYS-HIS (HCH) motif right at the end. It has been reported that CTR1 and CTR2 are physically associated with each other in the cell. We used the CRISPR-Cas9 technology to knock out either CTR1 or CTR2 in fully malignant HEK293T and OVCAR8 human ovarian cancer cells to investigate the interaction of CTR1 and CTR2. We report here that the level of CTR2 protein is markedly decreased in CTR1 knockout clones while the CTR2 transcript level remains unchanged. CTR2 was found to be highly ubiquitinated in the CTR1 knock out cells, and inhibition of the proteasome prevented the degradation of CTR2 when CTR1 was not present while inhibition of autophagy had no effect. Re-expression of CTR1 rescued CTR2 from degradation in the CTR1 knockout cells. We conclude that CTR1 is essential to maintain the stability of CTR2 and that in the absence of CTR1 CTR2 is degraded by the proteasome. This reinforces the concept that the functions of CTR1 and CTR2 are inter-dependent within the Cu homeostasis system.
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