Evidence map›Paper›PMID 35013287›Full record

ArticleCell death discovery2022

Microfluidic deep mutational scanning of the human executioner caspases reveals differences in structure and regulation.

Hridindu Roychowdhury, Philip A Romero

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Hridindu RoychowdhuryDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
Philip A RomeroDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA. promero2@wisc.edu.ORCID http://orcid.org/0000-0002-2586-7263
University of Wisconsin–Madison · US

Funding

Data-driven analysis of protein structure, function, and regulationR35GM119854 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI ROMERO, PHILIP ANTHONY · 2016 to 2020
$1.9M
NIGMS NIH HHS R35 GM119854U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 1R35GM119854
6 · The paper itself

Abstract

The human caspase family comprises 12 cysteine proteases that are centrally involved in cell death and inflammation responses. The members of this family have conserved sequences and structures, highly similar enzymatic activities and substrate preferences, and overlapping physiological roles. In this paper, we present a deep mutational scan of the executioner caspases CASP3 and CASP7 to dissect differences in their structure, function, and regulation. Our approach leverages high-throughput microfluidic screening to analyze hundreds of thousands of caspase variants in tightly controlled in vitro reactions. The resulting data provides a large-scale and unbiased view of the impact of amino acid substitutions on the proteolytic activity of CASP3 and CASP7. We use this data to pinpoint key functional differences between CASP3 and CASP7, including a secondary internal cleavage site, CASP7 Q196 that is not present in CASP3. Our results will open avenues for inquiry in caspase function and regulation that could potentially inform the development of future caspase-specific therapeutics.

Identifiers

PMID35013287
PMCPMC8748541
OpenAlexW4221107652

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.