Evidence map›Paper›PMID 31451653›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Activity-based ratiometric FRET probe reveals oncogene-driven changes in labile copper pools induced by altered glutathione metabolism.

Clive Yik-Sham Chung, Jessica M Posimo, Sumin Lee, Tiffany Tsang, Julianne M Davis, Donita C Brady, Christopher J Chang

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 156 citations in OpenAlex.

  1. Article
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  4. Review
  5. Article
  6. Simultaneous Imaging of CuAngewandte Chemie (International ed. in English) · 2026
    Article
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  10. Review
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  17. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
  18. A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Review

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Clive Yik-Sham ChungDepartment of Chemistry, University of California, Berkeley, CA 94720.
Jessica M PosimoDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Sumin LeeDepartment of Chemistry, University of California, Berkeley, CA 94720.
Tiffany TsangCell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Julianne M DavisCell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Donita C BradyDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; bradyd@pennmedicine.upenn.edu chrischang@berkeley.edu.ORCID 0000-0002-2786-2802
Christopher J ChangDepartment of Chemistry, University of California, Berkeley, CA 94720; bradyd@pennmedicine.upenn.edu chrischang@berkeley.edu.
University of Pennsylvania · USUniversity of California, Berkeley · USCancer Research Institute · USHoward Hughes Medical Institute · US

Funding

Molecular Imaging Probes To Study Redox BiologyR01GM079465 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2006 to 2026
$7.8M
Molecular and Cellular Mechanisms of Copper-Dependent Nutrient Signaling and MetabolismR35GM124749 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Donita C Brady · 2017 to 2026
$4.6M
Investigating paradoxical YAP activation as an emergent limitation to Cu chelation therapy in BRAF V600E-driven melanomaF31CA243294 · NCI · UNIVERSITY OF PENNSYLVANIA · PI TSANG, TIFFANY · 2019 to 2020
$67k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA243294NIGMS NIH HHS R01 GM079465NIGMS NIH HHS R35 GM124749
6 · The paper itself

Abstract

Copper is essential for life, and beyond its well-established ability to serve as a tightly bound, redox-active active site cofactor for enzyme function, emerging data suggest that cellular copper also exists in labile pools, defined as loosely bound to low-molecular-weight ligands, which can regulate diverse transition metal signaling processes spanning neural communication and olfaction, lipolysis, rest-activity cycles, and kinase pathways critical for oncogenic signaling. To help decipher this growing biology, we report a first-generation ratiometric fluorescence resonance energy transfer (FRET) copper probe, FCP-1, for activity-based sensing of labile Cu(I) pools in live cells. FCP-1 links fluorescein and rhodamine dyes through a Tris[(2-pyridyl)methyl]amine bridge. Bioinspired Cu(I)-induced oxidative cleavage decreases FRET between fluorescein donor and rhodamine acceptor. FCP-1 responds to Cu(I) with high metal selectivity and oxidation-state specificity and facilitates ratiometric measurements that minimize potential interferences arising from variations in sample thickness, dye concentration, and light intensity. FCP-1 enables imaging of dynamic changes in labile Cu(I) pools in live cells in response to copper supplementation/depletion, differential expression of the copper importer CTR1, and redox stress induced by manipulating intracellular glutathione levels and reduced/oxidized glutathione (GSH/GSSG) ratios. FCP-1 imaging reveals a labile Cu(I) deficiency induced by oncogene-driven cellular transformation that promotes fluctuations in glutathione metabolism, where lower GSH/GSSG ratios decrease labile Cu(I) availability without affecting total copper levels. By connecting copper dysregulation and glutathione stress in cancer, this work provides a valuable starting point to study broader cross-talk between metal and redox pathways in health and disease with activity-based probes.

Indexed as

Molecular Probe TechniquesCopperCopper Transporter 1FluoresceinFluorescence Resonance Energy TransferGlutathioneHEK293 CellsHeLa CellsHumansImage Processing, Computer-AssistedNeoplasmsOncogenesOxidation-ReductionOxidative StressRhodaminesSignal TransductionCopperCopper Transporter 1FluoresceinGlutathioneRhodaminesSLC31A1 protein, humanactivity-based sensingcancer metabolismfluorescent copper probeoxidative stressratiometric imaging

Identifiers

PMID31451653
PMCPMC6744846
OpenAlexW2970405392

What OpenQuestion holds

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Registered trials

None linked

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.