Evidence map›Paper›PMID 32366830›Full record

ArticleCell death & disease2020

Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation.

Yung-Hsuan Wu, Ting-Fang Chou, Leslie Young, Fu-Yi Hsieh, Hsuan-Yin Pan, Shu-Ting Mo, Shani Bialik Brown, Ruey-Hwa Chen, Adi Kimchi, Ming-Zong Lai

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Article
  8. RIPK1: A Promising Target for Intervention Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  9. Article
  10. Article
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  12. Review
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  15. Article
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  17. Article
  18. The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023
    Review
  19. Article
  20. Article
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 at 3 institutions in 2 countries.

Yung-Hsuan Wu *Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Ting-Fang Chou *Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Leslie YoungInstitute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Fu-Yi HsiehInstitute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Hsuan-Yin PanInstitute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Shu-Ting MoInstitute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Shani Bialik BrownDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
Ruey-Hwa ChenInstitute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
Adi KimchiDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
Ming-Zong LaiInstitute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan. mblai@gate.sinica.edu.tw.ORCID http://orcid.org/0000-0002-3237-4803
Institute of Molecular Biology, Academia Sinica · TWWeizmann Institute of Science · ILInstitute of Biological Chemistry, Academia Sinica · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Death-associated protein kinase 1 (DAPK1, DAPk, DAPK) is known for its involvement in apoptosis and autophagy-associated cell death. Here, we identified an unexpected function of DAPK1 in suppressing necroptosis. DAPK1-deficiency renders macrophages and dendritic cells susceptible to necroptotic death. We also observed an inhibitory role for DAPK1 in necroptosis in HT-29 cells, since knockdown or knockout of DAPK1 in such cells increased their sensitivity to necroptosis. Increased necroptosis was associated with enhanced formation of the RIPK1-RIPK3-MLKL complex in these DAPK1-deficient cells. We further found that DAPK1-deficiency led to decreased MAPK activated kinase 2 (MK2) activation and reduced RIPK1 S321 phosphorylation, with this latter representing a critical step controlling necrosome formation. Most TNF signaling pathways, including ERK, JNK, and AKT, were not regulated by DAPK. In contrast, DAPK bound p38 MAPK and selectively promoted p38 MAPK activation, resulting in enhanced MK2 phosphorylation. Our results reveal a novel role for DAPK1 in inhibiting necroptosis and illustrate an unexpected selectivity for DAPK1 in promoting p38 MAPK-MK2 activation. Importantly, our study suggests that modulation of necroptosis and p38/MK2-mediated inflammation may be achieved by targeting DAPK1.

Indexed as

NecroptosisAnimalsCaspase 8Cell SurvivalDeath-Associated Protein KinasesDown-RegulationEnzyme ActivationFas-Associated Death Domain ProteinGene Knockdown TechniquesHT29 CellsHumansIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2Mice, Inbred C57BLMice, KnockoutMyeloid CellsCaspase 8DAPK1 protein, humanDapk1 protein, mouseDeath-Associated Protein KinasesFas-Associated Death Domain ProteinIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2MLKL protein, humanp38 Mitogen-Activated Protein KinasesPhosphoserineProtein KinasesProtein Serine-Threonine KinasesReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanRIPK3 protein, humanTumor Necrosis Factor-alpha

Identifiers

PMID32366830
PMCPMC7198492
OpenAlexW3022694800

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.