Evidence map›Paper›PMID 29176560›Full record

ArticleNature communications2017

An activity-dependent proximity ligation platform for spatially resolved quantification of active enzymes in single cells.

Gang Li, Jeffrey E Montgomery, Mark A Eckert, Jae Won Chang, Samantha M Tienda, Ernst Lengyel, Raymond E Moellering

Abstract readEvaluation Study
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Article
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  4. Review
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  9. In Vivo Imaging of the Tumor-Associated Enzyme NCEH1 with a Covalent PET Probe.Angewandte Chemie (International ed. in English) · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. Ultrasensitive, multiplexed chemoproteomic profiling with soluble activity-dependent proximity ligation.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  14. Article
  15. Article
  16. 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

7 authors.

Gang LiDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Jeffrey E MontgomeryDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Mark A EckertDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, IL, 60637, USA.
Jae Won ChangDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Samantha M TiendaDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, IL, 60637, USA.
Ernst LengyelDepartment of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, IL, 60637, USA.ORCID http://orcid.org/0000-0001-8624-1507
Raymond E MoelleringDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA. rmoellering@uchicago.edu.ORCID http://orcid.org/0000-0002-2043-7838

Funding

VIRAL ONCOLOGY CORE FACILITYP30CA014599 · NCI · UNIVERSITY OF CHICAGO · PI MARK W. LINGEN · 1985 to 2026
$122.1M
Predoctoral Training Program in Chemistry & BiologyT32GM008720 · NIGMS · UNIVERSITY OF CHICAGO · PI PICCIRILLI, JOSEPH ANTHONY · 1999 to 2020
$4.7M
Regulation of Adhesion and Proteolysis in Ovarian CancerR01CA111882 · NCI · UNIVERSITY OF CHICAGO · PI LENGYEL, ERNST · 2006 to 2016
$2.8M
Targeting Transcription with Synthetic BiologicsDP2GM128199 · NIGMS · UNIVERSITY OF CHICAGO · PI MOELLERING, RAYMOND E · 2017 to 2017
$2.3M
Distribution, regulation and function of a novel lysine PTM in metabolic diseaseR00CA175399 · NCI · UNIVERSITY OF CHICAGO · PI MOELLERING, RAYMOND E · 2015 to 2017
$712k
NCI NIH HHS P30 CA014599NCI NIH HHS R00 CA175399NCI NIH HHS R01 CA111882NIGMS NIH HHS DP2 GM128199NIGMS NIH HHS T32 GM008720
6 · The paper itself

Abstract

Integration of chemical probes into proteomic workflows enables the interrogation of protein activity, rather than abundance. Current methods limit the biological contexts that can be addressed due to sample homogenization, signal-averaging, and bias toward abundant proteins. Here we report a platform that integrates family-wide chemical probes with proximity-dependent oligonucleotide amplification and imaging to quantify enzyme activity in native contexts with high spatial resolution. Application of this method, activity-dependent proximity ligation (ADPL), to serine hydrolase and cysteine protease enzymes enables quantification of differential enzyme activity resulting from endogenous changes in localization and expression. In a competitive format, small-molecule target engagement with endogenous proteins in live cells can be quantified. Finally, retention of sample architecture enables interrogation of complex environments such as cellular co-culture and patient samples. ADPL should be amenable to diverse probe and protein families to detect active enzymes at scale and resolution out of reach with current methods.

Indexed as

Cell Line, TumorCellsCysteine ProteasesEnzyme AssaysHumansHydrolasesOligonucleotidesProteomicsSingle-Cell AnalysisCysteine ProteasesHydrolasesOligonucleotides

Identifiers

PMID29176560
PMCPMC5701173

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.