Evidence map›Paper›PMID 39362992›Full record

ArticleCell death and differentiation2025

DNA damage-inducible transcript 3 positively regulates RIPK1-mediated necroptosis.

Rui Ni, Ting Cao, Xiaoyun Ji, Angel Peng, Zhuxu Zhang, Guo-Chang Fan, Peter Stathopulos, Subrata Chakrabarti, Zhaoliang Su, Tianqing Peng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. DDIT3 drives nucleus pulposus cell PANoptosis and intervertebral disc degeneration progression.Apoptosis : an international journal on programmed cell death · 2026
    Article
  10. Review
  11. Review
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

10 authors.

Rui Ni *International Genome Center, Jiangsu University, Zhenjiang, 212013, China.
Ting Cao *Institute for Cardiovascular Science, Soochow University, Suzhou, 215123, China.
Xiaoyun JiInternational Genome Center, Jiangsu University, Zhenjiang, 212013, China.
Angel PengDepartment of Pathology and Laboratory Medicine, Western University, London, ON, N6A 5C1, Canada.
Zhuxu ZhangLawson Health Research Institute, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Guo-Chang FanDepartment of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.ORCID 0000-0002-0439-8277
Peter StathopulosDepartment of Physiology and Pharmacology, Western University, London, ON, N6A 5C1, Canada.
Subrata ChakrabartiDepartment of Pathology and Laboratory Medicine, Western University, London, ON, N6A 5C1, Canada.ORCID 0000-0002-0208-1401
Zhaoliang SuInternational Genome Center, Jiangsu University, Zhenjiang, 212013, China. szI30@ujs.edu.cn.ORCID 0000-0002-5998-5575
Tianqing PengLawson Health Research Institute, London Health Sciences Centre, London, ON, N6A 5W9, Canada. tpeng2@uwo.ca.ORCID 0000-0002-5199-9016

Funding

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) RGPIN-2023-04573
6 · The paper itself

Abstract

DNA damage-inducible transcript 3 (DDIT3) is a well-known transcription factor that regulates the expression of apoptosis-related genes for promoting apoptosis during endoplasmic reticulum stress. Here, we report an unrecognized role of DDIT3 in facilitating necroptosis. DDIT3 directly binds and competitively prevents the p38 MAPK-MK2 interaction and thereby blocking MK2 activation while stimulating p38 MAPK activation. This blockage of MK2 activation initially prevents RIPK1 phosphorylation at Ser320 (inactivation), subsequently relieving its suppression of RIPK1 activation. Consequently, p38 MAPK facilitates RIPK1 phosphorylation at Ser166 (activation) through DDIT3 phosphorylation-related mechanisms, leading to necroptosis. Mechanistically, a 10-amino acid segment (Glu19-Val28) within DDIT3's N-terminus is identified to account for its pro-necroptotic function. In vivo studies demonstrate that forced expression of DDIT3 induces necroptosis, whereas deletion of DDIT3 alleviates necroptosis in mouse hearts under stress. These findings shed light on a novel regulatory mechanism by which DDIT3 promotes RIPK1 activation and subsequent necroptosis.

Indexed as

NecroptosisReceptor-Interacting Protein Serine-Threonine KinasesTranscription Factor CHOPAnimalsApoptosisHEK293 CellsHumansMiceMice, Inbred C57BLp38 Mitogen-Activated Protein KinasesPhosphorylationDdit3 protein, mousep38 Mitogen-Activated Protein KinasesReceptor-Interacting Protein Serine-Threonine KinasesRipk1 protein, mouseTranscription Factor CHOP

Identifiers

PMID39362992
PMCPMC11802725

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.