Evidence map›Paper›PMID 20723762›Full record

ArticleCell2010

Activation of specific apoptotic caspases with an engineered small-molecule-activated protease.

Daniel C Gray, Sami Mahrus, James A Wells

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

124 citing papers in PubMed, 216 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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64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Daniel C GrayDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Sami Mahrus
James A Wells
University of California, San Francisco · US

Funding

Global Analysis of Proteolysis in ApoptosisR01GM081051 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2007 to 2015
$2.8M
Direct Chemical Activators of CaspasesR01CA136779 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2009 to 2013
$1.5M
NCI NIH HHS CA136779NCI NIH HHS R01 CA136779NIGMS NIH HHS R01 GM081051
6 · The paper itself

Abstract

Apoptosis is a conserved cellular pathway that results in the activation of cysteine-aspartyl proteases, or caspases. To dissect the nonredundant roles of the executioner caspase-3, -6, and -7 in orchestrating apoptosis, we have developed an orthogonal protease to selectively activate each isoform in human cells. Our approach uses a split-tobacco etch virus (TEV) protease under small-molecule control, which we call the SNIPer, with caspase alleles containing genetically encoded TEV cleavage sites. These studies reveal that all three caspases are transiently activated but only activation of caspase-3 or -7 is sufficient to induce apoptosis. Proteomic analysis shown here and from others reveals that 20 of the 33 subunits of the 26S proteasome can be cut by caspases, and we demonstrate synergy between proteasome inhibition and dose-dependent caspase activation. We propose a model of proteolytic reciprocal negative regulation with mechanistic implications for the combined clinical use of proteasome inhibitors and proapoptotic drugs.

Indexed as

ApoptosisProtein EngineeringCaspase 3Caspase 6Caspase 7Cell LineDrug DesignEndopeptidasesEnzyme ActivationHumansIsoenzymesLeupeptinsProteasome Endopeptidase ComplexProteasome InhibitorsATP dependent 26S proteasebenzyloxycarbonylleucyl-leucyl-leucine aldehydeCaspase 3Caspase 6Caspase 7EndopeptidasesIsoenzymesLeupeptinsProteasome Endopeptidase ComplexProteasome InhibitorsTEV protease

Identifiers

PMID20723762
PMCPMC3689538
OpenAlexW2013069561

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.