Evidence map›Paper›PMID 23588206›Full record

ArticleExperimental cell research2013

Identification of a small molecule that induces ATG5-and-cathepsin-l-dependent cell death and modulates polyglutamine toxicity.

Hemant Varma, Nidhi M Gangadhar, Reka R Letso, Adam J Wolpaw, Rohitha Sriramaratnam, Brent R Stockwell

Open access · greenAbstract read
In one paragraph

Article in Experimental cell research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
1.8field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 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

6 authors at 1 institution in 1 country.

Hemant VarmaHoward Hughes Medical Institute, Department of Biological Sciences, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, United States.
Nidhi M GangadharHoward Hughes Medical Institute, Department of Biological Sciences, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States.
Reka R LetsoHoward Hughes Medical Institute, Department of Biological Sciences, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States.
Adam J WolpawHoward Hughes Medical Institute, Department of Biological Sciences, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States.
Rohitha SriramaratnamHoward Hughes Medical Institute, Department of Biological Sciences, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States.
Brent R StockwellHoward Hughes Medical Institute, Department of Biological Sciences, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States; Department of Chemistry, Columbia University, Northwest Corner Building, MC 4846, 550 West 120th Street, New York, NY 10027, United States. Electronic address: bstockwell@columbia.edu.
Howard Hughes Medical Institute · US

Funding

Chemical Genetic Profiling of Engineered Tumor CellsR01CA097061 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI STOCKWELL, BRENT R. · 2002 to 2016
$4.8M
Defining a novel trigger for apoptosisR01GM085081 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI STOCKWELL, BRENT R. · 2008 to 2011
$1.5M
Comparing HTS with Fragment-Based Design for B-Raf and the Ras-Raf InteractionR01CA161061 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI STOCKWELL, BRENT R. · 2011 to 2014
$1.0M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA097061NCI NIH HHS R01CA097061NCI NIH HHS R01 CA161061NCI NIH HHS R01CA161061NIGMS NIH HHS R01 GM085081NIGMS NIH HHS R01GM085081
6 · The paper itself

Abstract

Non-apoptotic cell death mechanisms are largely uncharacterized despite their importance in physiology and disease [1]. Here we sought to systematically identify non-apoptotic cell death pathways in mammalian cells. We screened 69,612 compounds for those that induce non-canonical cell death by counter screening in the presence of inhibitors of apoptosis and necrosis. We further selected compounds that require active protein synthesis for inducing cell death. Using this tiered approach, we identified NID-1 (Novel Inducer of Death-1), a small molecule that induces an active, energy-dependent cell death in diverse mammalian cell lines. NID-1-induced death required components of the autophagic machinery, including ATG5, and the lysosomal hydrolase cathepsin L, but was distinct from classical macroautophagy. Since macroautophagy can prevent cell death in several contexts, we tested and found that NID-1 suppressed cell death in a cell-based model of Huntington's disease, suggesting that NID-1 activates a specific pathway. Thus the discovery of NID-1 identifies a previously unexplored cell death pathway, and modulating this pathway may have therapeutic applications. Furthermore, these findings provide a proof-of-principle for using chemical screening to identify novel cell death paradigms.

Indexed as

AnimalsApoptosisAutophagyAutophagy-Related Protein 5Cathepsin LHigh-Throughput Screening AssaysHuntingtin ProteinMiceMicrotubule-Associated ProteinsNecrosisNerve Tissue ProteinsNuclear ProteinsPC12 CellsPeptidesProtein BiosynthesisRatsAtg5 protein, mouseAutophagy-Related Protein 5Cathepsin LHtt protein, ratHuntingtin ProteinMicrotubule-Associated ProteinsNerve Tissue ProteinsNID-1 compoundNuclear ProteinsPeptidespolyglutamineSmall Molecule LibrariesThiophenes

Identifiers

PMID23588206
PMCPMC3700633
OpenAlexW1976848492

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.