Evidence map›Paper›PMID 36252013›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Oxidation state-specific fluorescent copper sensors reveal oncogene-driven redox changes that regulate labile copper(II) pools.

Aidan T Pezacki, Carson D Matier, Xingxing Gu, Eric Kummelstedt, Sarah E Bond, Laura Torrente, Kelly L Jordan-Sciutto, Gina M DeNicola, Timothy A Su, Donita C Brady and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
9.4field-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

48 citing papers in PubMed, 96 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
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  7. Article
  8. Article
  9. Simultaneous Imaging of CuAngewandte Chemie (International ed. in English) · 2026
    Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. A primer on copper biology in the brain.Neurobiology of disease · 2025
    Review
  19. Article
  20. Article
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

11 authors at 5 institutions in 1 country.

Aidan T PezackiDepartment of Chemistry, University of California, Berkeley, CA 94720.ORCID 0000-0002-7321-462X
Carson D MatierDepartment of Chemistry, University of California, Berkeley, CA 94720.
Xingxing GuDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Eric KummelstedtDepartment of Chemistry, University of California, Berkeley, CA 94720.
Sarah E BondDepartment of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-8309-5206
Laura TorrenteDepartment of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612.ORCID 0000-0003-0343-0287
Kelly L Jordan-SciuttoDepartment of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-0827-1337
Gina M DeNicolaDepartment of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612.ORCID 0000-0001-6611-6696
Timothy A SuDepartment of Chemistry, University of California, Berkeley, CA 94720.ORCID 0000-0001-5934-3292
Donita C BradyDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-2786-2802
Christopher J ChangDepartment of Chemistry, University of California, Berkeley, CA 94720.ORCID 0000-0001-5732-9497
University of California, Berkeley · USUniversity of Pennsylvania · USMoffitt Cancer Center · USCancer Research Institute · USUniversity of California, Riverside · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
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
Structural biology and molecular biophysics training programT32GM132039 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Ben E. Black, Elizabeth Rhoades · 2019 to 2026
$3.3M
Chemical Probes to Study Methionine Redox BiologyR01GM139245 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2020 to 2026
$2.9M
Targeted Copper-based Therapeutics and ProbesF32GM122248 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SU, TIMOTHY · 2017 to 2019
$140k
NIEHS NIH HHS P30 ES013508NIGMS NIH HHS F32 GM122248NIGMS NIH HHS R01 GM079465NIGMS NIH HHS R01 GM139245NIGMS NIH HHS R35 GM124749NIGMS NIH HHS T32 GM132039
6 · The paper itself

Abstract

Copper is an essential metal nutrient for life that often relies on redox cycling between Cu(I) and Cu(II) oxidation states to fulfill its physiological roles, but alterations in cellular redox status can lead to imbalances in copper homeostasis that contribute to cancer and other metalloplasias with metal-dependent disease vulnerabilities. Copper-responsive fluorescent probes offer powerful tools to study labile copper pools, but most of these reagents target Cu(I), with limited methods for monitoring Cu(II) owing to its potent fluorescence quenching properties. Here, we report an activity-based sensing strategy for turn-on, oxidation state-specific detection of Cu(II) through metal-directed acyl imidazole chemistry. Cu(II) binding to a metal and oxidation state-specific receptor that accommodates the harder Lewis acidity of Cu(II) relative to Cu(I) activates the pendant dye for reaction with proximal biological nucleophiles and concomitant metal ion release, thus avoiding fluorescence quenching. Copper-directed acyl imidazole 649 for Cu(II) (CD649.2) provides foundational information on the existence and regulation of labile Cu(II) pools, including identifying divalent metal transporter 1 (DMT1) as a Cu(II) importer, labile Cu(II) increases in response to oxidative stress induced by depleting total glutathione levels, and reciprocal increases in labile Cu(II) accompanied by decreases in labile Cu(I) induced by oncogenic mutations that promote oxidative stress.

Indexed as

CopperFluorescent DyesGlutathioneImidazolesOncogenesOxidation-ReductionCopperFluorescent DyesGlutathioneImidazolesactivity-based sensingcancer metabolismfluorescent copper probeoxidative stresstransition metal signaling

Identifiers

PMID36252013
PMCPMC9621372
OpenAlexW4306641898

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.