Evidence map›Paper›PMID 42161275›Full record

ArticleNeuron2026

ATF2 phosphorylation is a core transcriptional driver of neuron apoptosis.

Jorge Gómez-Deza, Matthew Nebiyou, Lara H El Touny, Mor R Alkaslasi, Zhenyu Zuo, Josette J Wlaschin, Francisco M Nadal-Nicolás, Alexandra Stavsky, Xiaotian Zhang, Anastasia L Slavutsky and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Jorge Gómez-DezaEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; Department of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Fox Chase Cancer Center, Cancer Signaling and Microenvironment Program, Philadelphia, PA, USA. Electronic address: jorge.gomez-deza@temple.edu.
Matthew NebiyouEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Lara H El TounyFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Mor R AlkaslasiEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Zhenyu ZuoEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Josette J WlaschinEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Francisco M Nadal-NicolásNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Alexandra StavskyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Xiaotian ZhangCenter for Neural Development and Repair, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Anastasia L SlavutskyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Ariel Y ZhangDepartment of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Fox Chase Cancer Center, Cancer Signaling and Microenvironment Program, Philadelphia, PA, USA.
Eliza Y H LloydEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Peter M HayashiDepartment of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Fox Chase Cancer Center, Cancer Signaling and Microenvironment Program, Philadelphia, PA, USA.
Nathan AshbyEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Mariella G BrueckDepartment of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Fox Chase Cancer Center, Cancer Signaling and Microenvironment Program, Philadelphia, PA, USA.
Mira SohnEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Ryan K DaleEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Gareth M ThomasCenter for Neural Development and Repair, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Department of Neural Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Wei LiNational Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Ken Chih-Chien ChengFunctional Genomics Laboratory, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Pedro P RochaEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Claire E Le PichonEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: claire.lepichon@nih.gov.

Funding

Functions of the Synaptic Ribbon in Retinal NeuronsZIAEY000488 · NEI · NATIONAL EYE INSTITUTE · PI LI, WEI · 2009 to 2025
$22.0M
The neuronal stress response in neurodegenerative disease and painZIAHD008966 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LE PICHON, CLAIRE · 2017 to 2025
$17.1M
Genome 3D organization as a determinant of cell-fate decisionsZIAHD008975 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI ROCHA, PEDRO · 2018 to 2025
$10.4M
Trans-NIH RNAi Facility (TNRF)ZICTR000041 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI CHENG, KEN · 2015 to 2025
$9.4M
Regulation of Axonal Signaling by PalmitoylationR01NS094402 · NINDS · TEMPLE UNIV OF THE COMMONWEALTH · PI THOMAS, GARETH · 2015 to 2025
$3.7M
Intramural NIH HHS ZIA EY000488Intramural NIH HHS ZIA HD008966Intramural NIH HHS ZIA HD008975Intramural NIH HHS ZIC TR000041NINDS NIH HHS R01 NS094402
6 · The paper itself

Abstract

Neuronal apoptosis is a key feature of neurodegenerative diseases. Considerable efforts have been made to target this pathway; however, the underlying molecular mechanisms remain incompletely understood. Here, we conducted an unbiased, genome-wide CRISPR inhibition screen in human neurons to discover genes required for cell death. We uncover a multitude of targets required for neuronal apoptosis, some known and many previously unidentified. Among them, three stood out as members of a pro-death cascade: dual leucine zipper kinase (DLK or MAP3K12) and the transcription factors JUN and the lesser-known activating transcription factor 2 (ATF2). Through mechanistic studies, we demonstrate that ATF2 phosphorylation by MAP3 kinases is a critical step in neuronal apoptosis. Surprisingly, JUN phosphorylation is not required. Conversion of the MAP3 kinase signal into a pro-apoptotic transcriptional response requires phospho-ATF2 to upregulate JUN. We show that interfering with ATF2 function prevents neuronal apoptosis in vitro and in vivo. Our work posits ATF2 as a promising target for a wide range of neurodegenerative disorders.

Indexed as

Activating Transcription Factor 2ApoptosisNeuronsAnimalsCells, CulturedHumansMAP Kinase Kinase KinasesMicePhosphorylationTranscription, GeneticActivating Transcription Factor 2ATF2 protein, humanMAP Kinase Kinase Kinasesmitogen-activated protein kinase kinase kinase 12ATF2CRISPRi screencytoskeletal stressDLKJUNLZKMAP3K12neuronal apoptosisneuron deathneuron injury signaling

Identifiers

PMID42161275
PMCPMC13192301

What OpenQuestion holds

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Registered trials

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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.