Evidence map›Paper›PMID 35257663›Full record

ArticleeLife2022

Cell-surface tethered promiscuous biotinylators enable comparative small-scale surface proteomic analysis of human extracellular vesicles and cells.

Lisa L Kirkemo, Susanna K Elledge, Jiuling Yang, James R Byrnes, Jeff E Glasgow, Robert Blelloch, James A Wells

Abstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Proteomics-Based Approaches to Decipher the Molecular Strategies ofJournal of fungi (Basel, Switzerland) · 2025
    Review
  9. Article
  10. Article
  11. Science advances · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Cell-surface Milieu Remodeling in Human Dendritic Cell Activation.Journal of immunology (Baltimore, Md. : 1950) · 2024
    Article
  18. Article
  19. Article
  20. Review
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.

Lisa L Kirkemo *Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.ORCID 0000-0003-1686-6987
Susanna K Elledge *Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-9621-3881
Jiuling YangDepartment of Urology, University of California, San Francisco, San Francisco, United States.
James R ByrnesDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.ORCID 0000-0003-0297-1209
Jeff E GlasgowDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.
Robert BlellochDepartment of Urology, University of California, San Francisco, San Francisco, United States.ORCID 0000-0002-1975-0798
James A WellsDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States.ORCID 0000-0001-8267-5519

Funding

Surfaceomic technologies and antibodies to probe cell surface proteomes and their interactomes at unprecedented small scale and high-resolutionR35GM122451 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2017 to 2026
$5.3M
Mechanisms of Exosome Driven Immunoregulation of Cancer ProgressionU01CA244452 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLELLOCH, ROBERT, FONG, LAWRENCE · 2019 to 2022
$4.1M
New protein engineering-based tools and technologies for characterizing cell surface proteolysis in cancer cells for novel neo-epitope biomarkers and drug targetsR01CA248323 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES A WELLS · 2020 to 2026
$2.6M
Mechanistic Insights and Diagnostic Applications for Hypoxia-Induced Vasorin in Pancreatic CancerF31CA247527 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KIRKEMO, LISA · 2020 to 2022
$100k
NCI NIH HHS F31 CA247527NCI NIH HHS R01 CA248323NCI NIH HHS U01 CA244452NIGMS NIH HHS R35 GM122451
6 · The paper itself

Abstract

Characterization of cell surface proteome differences between cancer and healthy cells is a valuable approach for the identification of novel diagnostic and therapeutic targets. However, selective sampling of surface proteins for proteomics requires large samples (>10e6 cells) and long labeling times. These limitations preclude analysis of material-limited biological samples or the capture of rapid surface proteomic changes. Here, we present two labeling approaches to tether exogenous peroxidases (APEX2 and HRP) directly to cells, enabling rapid, small-scale cell surface biotinylation without the need to engineer cells. We used a novel lipidated DNA-tethered APEX2 (DNA-APEX2), which upon addition to cells promoted cell agnostic membrane-proximal labeling. Alternatively, we employed horseradish peroxidase (HRP) fused to the glycan-binding domain of wheat germ agglutinin (WGA-HRP). This approach yielded a rapid and commercially inexpensive means to directly label cells containing common N-Acetylglucosamine (GlcNAc) and sialic acid glycans on their surface. The facile WGA-HRP method permitted high surface coverage of cellular samples and enabled the first comparative surface proteome characterization of cells and cell-derived small extracellular vesicles (EVs), leading to the robust quantification of 953 cell and EV surface annotated proteins. We identified a newly recognized subset of EV-enriched markers, as well as proteins that are uniquely upregulated on Myc oncogene-transformed prostate cancer EVs. These two cell-tethered enzyme surface biotinylation approaches are highly advantageous for rapidly and directly labeling surface proteins across a range of material-limited sample types.

Indexed as

Extracellular VesiclesProteomicsHorseradish PeroxidaseHumansMaleProteomeWheat Germ AgglutininsHorseradish PeroxidaseProteomeWheat Germ AgglutininsAPEX2biochemistrycancer biologycell surfacechemical biologyextracellular vesicleHRPhumanproteomicssurfaceomics

Identifiers

PMID35257663
PMCPMC8983049

What OpenQuestion holds

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LicenceCC BY
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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.