Evidence map›Paper›PMID 30821975›Full record

ArticleJournal of the American Chemical Society2019

Designing a Green Fluorogenic Protease Reporter by Flipping a Beta Strand of GFP for Imaging Apoptosis in Animals.

Qiang Zhang, Antonino Schepis, Hai Huang, Junjiao Yang, Wen Ma, Joaquim Torra, Shao-Qing Zhang, Lina Yang, Haifan Wu, Santi Nonell and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
12.7field-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

61 citing papers in PubMed, 98 citations in OpenAlex.

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  8. A programmable genetic platform for engineering noninvasive biosensors.bioRxiv : the preprint server for biology · 2025
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  13. Protein Engineering for Spatiotemporally Resolved Cellular Monitoring.Annual review of analytical chemistry (Palo Alto, Calif.) · 2025
    Review
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1 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

14 authors at 5 institutions in 3 countries.

Qiang ZhangDepartment of Pharmaceutical Chemistry , University of California-San Francisco , San Francisco , California 94158 , United States.
Antonino SchepisCardiovascular Research Institute, University of California-San Francisco , San Francisco , California 94158 , United States.
Hai HuangCardiovascular Research Institute, University of California-San Francisco , San Francisco , California 94158 , United States.
Junjiao YangDepartment of Pharmaceutical Chemistry , University of California-San Francisco , San Francisco , California 94158 , United States.
Wen MaDepartment of Chemistry and Biochemistry , University of California San Diego , La Jolla , California 92093 , United States.
Joaquim TorraDepartment of Pharmaceutical Chemistry , University of California-San Francisco , San Francisco , California 94158 , United States.
Shao-Qing ZhangDepartment of Neurology, Harvard Medical School and MassGeneral Institute for Neurodegenerative Disease , Massachusetts General Hospital , Charlestown , Massachusetts 02129 , United States.
Lina YangBio-Medical Center, College of Life Science and Technology , Huazhong Agricultural University , Wuhan , Hubei 430070 , China.
Haifan WuDepartment of Pharmaceutical Chemistry , University of California-San Francisco , San Francisco , California 94158 , United States.ORCID 0000-0002-2050-9950
Santi NonellInstitut Químic de Sarrià, Universitat Ramon Llull , Via Augusta 390 , 08017 Barcelona , Spain.ORCID 0000-0002-8900-5291
Zhiqiang DongBio-Medical Center, College of Life Science and Technology , Huazhong Agricultural University , Wuhan , Hubei 430070 , China.
Thomas B KornbergCardiovascular Research Institute, University of California-San Francisco , San Francisco , California 94158 , United States.
Shaun R CoughlinCardiovascular Research Institute, University of California-San Francisco , San Francisco , California 94158 , United States.
Xiaokun ShuDepartment of Pharmaceutical Chemistry , University of California-San Francisco , San Francisco , California 94158 , United States.ORCID 0000-0001-9248-7095
University of California, San Francisco · USHuazhong Agricultural University · CNHarvard University · USInstitut Químic de Sarrià · ESUniversity of California San Diego · US

Funding

MOLECULAR AND CELLULAR BASIS OF CARDIOVASCULAR DISEASET32HL007731 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian L Black · 1992 to 2026
$12.4M
Molecular Mechanisms in DevelopmentR35GM122548 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI THOMAS B. KORNBERG · 2017 to 2026
$8.8M
Deciphering the relationship between structure, dynamics and function in helical bundle proteinsR35GM122603 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WILLIAM DEGRADO · 2017 to 2026
$7.1M
MOLECULAR GENETICS OF CARDIAC CELL DIFFERENTIATIONR01HL054737 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COUGHLIN, SHAUN R. · 1996 to 2015
$5.4M
Structural Basis of Protease-Activated Receptor FunctionR01HL121387 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COUGHLIN, SHAUN R., KOBILKA, BRIAN K · 2014 to 2017
$2.9M
Rational design of a genetically encoded infrared fluorescent protease reporterR01GM115399 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHU, XIAOKUN · 2015 to 2018
$1.3M
NHLBI NIH HHS R01 HL054737NHLBI NIH HHS R01 HL121387NHLBI NIH HHS T32 HL007731NIGMS NIH HHS R01 GM115399NIGMS NIH HHS R35 GM122548NIGMS NIH HHS R35 GM122603
6 · The paper itself

Abstract

A family of proteases called caspases mediate apoptosis signaling in animals. We report a GFP-based fluorogenic protease reporter, dubbed "FlipGFP", by flipping a beta strand of the GFP. Upon protease activation and cleavage, the beta strand is restored, leading to reconstitution of the GFP and fluorescence. FlipGFP-based TEV protease reporter achieves 100-fold fluorescence change. A FlipGFP-based executioner caspase reporter visualized apoptosis in live zebrafish embryos with spatiotemporal resolution. FlipGFP also visualized apoptotic cells in the midgut of Drosophila. Thus, the FlipGFP-based caspase reporter will be useful for monitoring apoptosis during animal development and for designing reporters of proteases beyond caspases. The design strategy can be further applied to a red fluorescent protein for engineering a red fluorogenic protease reporter.

Indexed as

ApoptosisMolecular ImagingAnimalsDrosophila melanogasterGenes, ReporterGreen Fluorescent ProteinsHEK293 CellsHeLa CellsHumansPeptide HydrolasesProtein Conformation, beta-StrandGreen Fluorescent ProteinsPeptide Hydrolases

Identifiers

PMID30821975
PMCPMC6486793
OpenAlexW2919962130

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.