ArticleMolecular and cellular biology2012
A novel role for copper in Ras/mitogen-activated protein kinase signaling.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
184 citing papers in PubMed, 3 syntheses or guidelines pooled it, 310 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Heavy metals in biological samples of cancer patients: a systematic literature review.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Pooled it
- Pooled it
- Research progress of pancreatic cancer based on ferroptosis-cuproptosis interaction (Review).Oncology letters · 2026Review
- Effects of cuproptosis and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2026Review
- Antiproliferation and Anti-invasion Activity of Binuclear Copper(II) Complex in BRAFi-Resistant Melanoma Cells.ACS pharmacology & translational science · 2026Article
- 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 depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.Nature cancer · 2026Article
- Targeting Copper in Cancer: Chelators to Counteract Cuproplasia and Ionophores to Promote Cuproptosis.Journal of medicinal chemistry · 2026Review
- Copper-based metal-organic frameworks: applications and prospects in cancer diagnosis and therapy.RSC advances · 2026Review
- Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems.Chemical & biomedical imaging · 2026Article
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- The PBAF chromatin remodeling complex contributes to metal homeostasis through MTF1 regulation.Metallomics : integrated biometal science · 2026Article
- Copper modulates cell fate through the PLK1-FOXO3a-β-catenin signaling pathway by differentially regulating cuproptosis and EMT.Apoptosis : an international journal on programmed cell death · 2026Article
- Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine.Pharmaceutics · 2026Review
- Research Progress on Copper Metabolism, Cuprotosis, and Their Regulatory Mechanism in Tumor Diagnosis and Treatment.Cancer management and research · 2026Review
- The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.Molecular and cellular biology · 2026Article
- Protective Functions of β-Alanyl-L-Histidine and Glycyl-L-Histidyl-L-Lysine Glycoconjugates and Copper in Concert.Antioxidants (Basel, Switzerland) · 2025Review
124 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Copper (Cu) is essential for development and proliferation, yet the cellular requirements for Cu in these processes are not well defined. We report that Cu plays an unanticipated role in the mitogen-activated protein (MAP) kinase pathway. Ablation of the Ctr1 high-affinity Cu transporter in flies and mouse cells, mutation of Ctr1, and Cu chelators all reduce the ability of the MAP kinase kinase Mek1 to phosphorylate the MAP kinase Erk. Moreover, mice bearing a cardiac-tissue-specific knockout of Ctr1 are deficient in Erk phosphorylation in cardiac tissue. in vitro investigations reveal that recombinant Mek1 binds two Cu atoms with high affinity and that Cu enhances Mek1 phosphorylation of Erk in a dose-dependent fashion. Coimmunoprecipitation experiments suggest that Cu is important for promoting the Mek1-Erk physical interaction that precedes the phosphorylation of Erk by Mek1. These results demonstrate a role for Ctr1 and Cu in activating a pathway well known to play a key role in normal physiology and in cancer.
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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.