Evidence map›Paper›PMID 28141794›Full record

ArticleCell death and differentiation2017

Death-associated protein kinase 1 phosphorylates NDRG2 and induces neuronal cell death.

Mi-Hyeon You, Byeong Mo Kim, Chun-Hau Chen, Michael J Begley, Lewis C Cantley, Tae Ho Lee

Abstract read
In one paragraph

Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
–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

44 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  4. Article
  5. Article
  6. Epigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  7. Review
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  15. Current neuropharmacology · 2024
    Article
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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.

Mi-Hyeon YouDivision of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Byeong Mo KimDivision of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Chun-Hau ChenDivision of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Michael J BegleyDivision of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Lewis C CantleyDivision of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Tae Ho LeeDivision of Gerontology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Funding

THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
A Natonal Resource for Postmortem Brain ResearchR24MH068855 · NIMH · MC LEAN HOSPITAL (BELMONT, MA) · PI BENES, FRANCINE M. · 2003 to 2012
$14.8M
Pin1-dependent telomere regulation in aging and Alzheimer's diseaseR00AG033104 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LEE, TAE HO · 2011 to 2013
$733k
NIA NIH HHS P50 AG005134NIA NIH HHS R00 AG033104NIMH NIH HHS R24 MH068855
6 · The paper itself

Abstract

Death-associated protein kinase 1 (DAPK1) has been shown to have important roles in neuronal cell death in several model systems and has been implicated in multiple diseases, including Alzheimer's disease (AD). However, little is known about the molecular mechanisms by which DAPK1 signals neuronal cell death. In this study, N-myc downstream-regulated gene 2 (NDRG2) was identified as a novel substrate of DAPK1 using phospho-peptide library screening. DAPK1 interacted with NDRG2 and directly phosphorylated the Ser350 residue in vitro and in vivo. Moreover, DAPK1 overexpression increased neuronal cell death through NDRG2 phosphorylation after ceramide treatment. In contrast, inhibition of DAPK1 by overexpression of a DAPK1 kinase-deficient mutant and small hairpin RNA, or by treatment with a DAPK1 inhibitor significantly decreased neuronal cell death, and abolished NDRG2 phosphorylation in cell culture and in primary neurons. Furthermore, NDRG2-mediated cell death by DAPK1 was required for a caspase-dependent poly-ADP-ribose polymerase cleavage. In addition, DAPK1 ablation suppressed ceramide-induced cell death in mouse brain and neuronal cell death in Tg2576 APPswe-overexpressing mice. Finally, levels of phosphorylated NDRG2 Ser350 and DAPK1 were significantly increased in human AD brain samples. Thus, phosphorylation of NDRG2 on Ser350 by DAPK1 is a novel mechanism activating NDRG2 function and involved in neuronal cell death regulation in vivo.

Indexed as

Adaptor Proteins, Signal TransducingAlzheimer DiseaseAmino Acid Chloromethyl KetonesAnimalsApoptosisBrainCaspase 3Cells, CulturedCeramidesDeath-Associated Protein KinasesHEK293 CellsHeLa CellsHumansMiceMice, Inbred C57BLMice, TransgenicAdaptor Proteins, Signal TransducingAmino Acid Chloromethyl Ketonesbenzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketoneCaspase 3CeramidesDapk1 protein, mouseDeath-Associated Protein KinasesNdr2 protein, mousePoly(ADP-ribose) PolymerasesProteins

Identifiers

PMID28141794
PMCPMC5299707

What OpenQuestion holds

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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.