Evidence map›Paper›PMID 25183729›Full record

ArticleInfection and immunity2014

DAP1, a negative regulator of autophagy, controls SubAB-mediated apoptosis and autophagy.

Kinnosuke Yahiro, Hiroyasu Tsutsuki, Kohei Ogura, Sayaka Nagasawa, Joel Moss, Masatoshi Noda

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Modeling Shiga toxin-induced human renal-specific microvascular injury.Integrative biology : quantitative biosciences from nano to macro · 2024
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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 at 2 institutions in 2 countries.

Kinnosuke YahiroDepartment of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan yahirok@faculty.chiba-u.jp.
Hiroyasu TsutsukiDepartment of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kohei OguraDepartment of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Sayaka NagasawaDepartment of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Joel MossCardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Masatoshi NodaDepartment of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Chiba University · JPNational Institutes of Health · US

Funding

Intramural NIH HHS
6 · The paper itself

Abstract

Autophagy and apoptosis play critical roles in cellular homeostasis and survival. Subtilase cytotoxin (SubAB), produced by non-O157 type Shiga-toxigenic Escherichia coli (STEC), is an important virulence factor in disease. SubAB, a protease, cleaves a specific site on the endoplasmic reticulum (ER) chaperone protein BiP/GRP78, leading to ER stress, and induces apoptosis. Here we report that in HeLa cells, activation of a PERK (RNA-dependent protein kinase [PKR]-like ER kinase)-eIF2α (α subunit of eukaryotic initiation factor 2)-dependent pathway by SubAB-mediated BiP cleavage negatively regulates autophagy and induces apoptosis through death-associated protein 1 (DAP1). We found that SubAB treatment decreased the amounts of autophagy markers LC3-II and p62 as well as those of mTOR (mammalian target of rapamycin) signaling proteins ULK1 and S6K. These proteins showed increased expression levels in PERK knockdown or DAP1 knockdown cells. In addition, depletion of DAP1 in HeLa cells dramatically inhibited the SubAB-stimulated apoptotic pathway: SubAB-induced Bax/Bak conformational changes, Bax/Bak oligomerization, cytochrome c release, activation of caspases, and poly(ADP-ribose) polymerase (PARP) cleavage. These results show that DAP1 is a key regulator, through PERK-eIF2α-dependent pathways, of the induction of apoptosis and reduction of autophagy by SubAB.

Indexed as

ApoptosisApoptosis Regulatory ProteinsAutophagybcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinEndoplasmic Reticulum Chaperone BiPEscherichia coliEscherichia coli ProteinsGene Expression RegulationHeLa CellsHumansSubtilisinsApoptosis Regulatory ProteinsBAK1 protein, humanBAX protein, humanbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinDAP protein, humanEndoplasmic Reticulum Chaperone BiPEscherichia coli ProteinsHSPA5 protein, humansubtilase cytotoxin, E coliSubtilisins

Identifiers

PMID25183729
PMCPMC4249318
OpenAlexW2136421195

What OpenQuestion holds

Textmetadata
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.