Evidence map›Paper›PMID 29125730›Full record

ArticleACS chemical biology2018

Development of a Protease Biosensor Based on a Dimerization-Dependent Red Fluorescent Protein.

Aaron C Mitchell, Spencer C Alford, Sean A Hunter, Deepti Kannan, R Andres Parra Sperberg, Cheryl H Chang, Jennifer R Cochran

Abstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

8 citing papers in PubMed, 20 citations in OpenAlex.

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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 1 institution in 1 country.

Aaron C MitchellDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.ORCID 0000-0002-7164-1943
Spencer C AlfordDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.
Sean A HunterCancer Biology Program, Stanford University , Stanford, California 94305, United States.
Deepti KannanDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.
R Andres Parra SperbergDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.
Cheryl H ChangDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.
Jennifer R CochranDepartment of Bioengineering, Stanford University , Stanford, California 94305, United States.
Stanford University · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Graduate Training Program in BiotechnologyT32GM008412 · NIGMS · STANFORD UNIVERSITY · PI COCHRAN, JENNIFER R · 1991 to 2020
$5.5M
Engineered HGF-NK1 antagonists for Met-targeted cancer imaging and therapyR01CA151706 · NCI · STANFORD UNIVERSITY · PI COCHRAN, JENNIFER R · 2010 to 2014
$1.6M
NCI NIH HHS R01 CA151706NCI NIH HHS T32 CA009302NIGMS NIH HHS T32 GM008412
6 · The paper itself

Abstract

Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address this need, we developed a matriptase-sensitive protein biosensor based on a dimerization-dependent red fluorescent protein (ddRFP) reporter system. In this platform, two adjoining protein domains, connected by a protease-labile linker, produce fluorescence when assembled and are nonfluorescent when the linker is cleaved by matriptase. A panel of ddRFP-based matriptase biosensor designs was created that contained different linker lengths between the protein domains. These constructs were characterized for linker-specific cleavage, matriptase activity, and matriptase selectivity; a biosensor containing a RSKLRVGGH linker (termed B4) was expressed at high yields and displayed both high catalytic efficiency and matriptase specificity. This biosensor detects matriptase inhibition by soluble and yeast cell surface expressed inhibitor domains with up to a 5-fold dynamic range and also detects matriptase activity expressed by human cancer cell lines. In addition to matriptase, we highlight a strategy that can be used to create effective biosensors for quantifying activity and inhibition of other proteases of interest.

Indexed as

Biosensing TechniquesBlotting, WesternCell Line, TumorDrug Evaluation, PreclinicalEscherichia coliHumansLuminescent ProteinsPeptide HydrolasesProtein MultimerizationRed Fluorescent ProteinSerine EndopeptidasesSerine Proteinase InhibitorsStructure-Activity RelationshipLuminescent ProteinsmatriptasePeptide HydrolasesRed Fluorescent ProteinSerine EndopeptidasesSerine Proteinase Inhibitors

Identifiers

PMID29125730
PMCPMC6453536
OpenAlexW2767964081

What OpenQuestion holds

Textmetadata
LicenceTDM
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.