Evidence map›Paper›PMID 27846469›Full record

ArticleScience (New York, N.Y.)2016

A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1.

Yingfei Wang, Ran An, George K Umanah, Hyejin Park, Kalyani Nambiar, Stephen M Eacker, BongWoo Kim, Lei Bao, Maged M Harraz, Calvin Chang and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 246 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
246citing papers in PubMed, 1 pooled it
12.9field-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

246 citing papers in PubMed, 1 synthesis or guideline pooled it, 397 citations in OpenAlex.

  1. Pooled it
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  12. PARP1 deficiency mitigates amyloid pathology, neurodegeneration, and cognitive decline in a familial Alzheimer's disease model.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Review
  14. MIF Tautomerase Inhibition Protects Neurons From Immune-Mediated Cell Death.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Article
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186 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 1 country.

Yingfei WangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. tdawson@jhmi.edu vdawson1@jhmi.edu yingfei.wang@utsouthwestern.edu.
Ran AnNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
George K UmanahNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hyejin ParkNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kalyani NambiarNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stephen M EackerNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
BongWoo KimDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lei BaoDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Maged M HarrazNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Calvin ChangNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rong ChenNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jennifer E WangDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Tae-In KamNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jun Seop JeongDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zhi XieDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stewart NeifertNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jiang QianDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Shaida A AndrabiNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Seth BlackshawSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Heng ZhuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hongjun SongNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Guo-Li MingNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. tdawson@jhmi.edu vdawson1@jhmi.edu yingfei.wang@utsouthwestern.edu.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. tdawson@jhmi.edu vdawson1@jhmi.edu yingfei.wang@utsouthwestern.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USThe University of Texas Southwestern Medical Center · USHigh Throughput Biology (United States) · US

Funding

UNDERSTANDING NO SIGNALING RESULTING IN NEUROPROTECTION.P50DA000266 · NIDA · JOHNS HOPKINS UNIVERSITY · PI SNYDER, SOLOMON H. · 1985 to 2017
$45.2M
Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8M
Poly (ADP-Ribose) and AIF in Neuronal InjuryR01NS067525 · NINDS · JOHNS HOPKINS UNIVERSITY · PI VALINA L. DAWSON, Ted M. Dawson · 2010 to 2026
$6.0M
Parthanatos, AIF and PAAN-1 in Neuronal InjuryR37NS067525 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DAWSON, TED M., DAWSON, VALINA L. · 2015 to 2021
$5.3M
The role of a novel AIF-associated nuclease PAAN1 in neuronal injuryR00NS078049 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI WANG, YINGFEI · 2015 to 2017
$747k
The role of a novel AIF-associated nuclease PAAN1 in neuronal injuryK99NS078049 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, YINGFEI · 2012 to 2013
$190k
NIDA NIH HHS P50 DA000266NINDS NIH HHS K99 NS078049NINDS NIH HHS P50 NS038377NINDS NIH HHS R00 NS078049NINDS NIH HHS R01 NS067525NINDS NIH HHS R37 NS067525
6 · The paper itself

Abstract

Inhibition or genetic deletion of poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) is protective against toxic insults in many organ systems. The molecular mechanisms underlying PARP-1-dependent cell death involve release of mitochondrial apoptosis-inducing factor (AIF) and its translocation to the nucleus, which results in chromatinolysis. We identified macrophage migration inhibitory factor (MIF) as a PARP-1-dependent AIF-associated nuclease (PAAN). AIF was required for recruitment of MIF to the nucleus, where MIF cleaves genomic DNA into large fragments. Depletion of MIF, disruption of the AIF-MIF interaction, or mutation of glutamic acid at position 22 in the catalytic nuclease domain blocked MIF nuclease activity and inhibited chromatinolysis, cell death induced by glutamate excitotoxicity, and focal stroke. Inhibition of MIF's nuclease activity is a potential therapeutic target for diseases caused by excessive PARP-1 activation.

Indexed as

ApoptosisDNA CleavageDNA DamageActive Transport, Cell NucleusAmino Acid SequenceAnimalsApoptosis Inducing FactorBase SequenceCatalytic DomainCell NucleusChromatinDeoxyribonucleasesDNA FragmentationDNA, Single-StrandedGlutamic AcidHeLa CellsApoptosis Inducing FactorChromatinDeoxyribonucleasesDNA, Single-StrandedGlutamic AcidIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMIF protein, humanPoly (ADP-Ribose) Polymerase-1

Identifiers

PMID27846469
PMCPMC5134926
OpenAlexW2529744299

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.