Evidence map›Paper›PMID 39955274›Full record

ArticleCell death & disease2025

The integrated stress response engages a cell-autonomous, ligand-independent, DR5-driven apoptosis switch.

Francesca Zappa, Nerea L Muniozguren, Julia E Conrad, Diego Acosta-Alvear

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
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  11. Article
  12. Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023
    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

4 authors.

Francesca Zappa *Department of Cellular, Molecular, and Developmental Biology, University of California, Santa Barbara, USA.ORCID http://orcid.org/0000-0003-1263-3828
Nerea L Muniozguren *Department of Cellular, Molecular, and Developmental Biology, University of California, Santa Barbara, USA.ORCID http://orcid.org/0000-0001-6553-6277
Julia E ConradAltos Labs Bay Area Institute of Science, Altos Labs, Inc., Redwood City, USA.
Diego Acosta-AlvearDepartment of Cellular, Molecular, and Developmental Biology, University of California, Santa Barbara, USA. dacostaalvear@altoslabs.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The integrated stress response (ISR) is a fundamental signaling network that leverages the cell's biosynthetic capacity against different stresses to restore homeostasis. However, when homeostasis is unattainable, the ISR switches to drive cell death and eliminate irreparably damaged cells. Previous work has shown that persistent activity of the ISR kinase PERK during unyielding endoplasmic reticulum (ER) stress induces apoptosis downstream of death receptor 5 (DR5) [1]. ER stress provides activating signals that engage the ectodomain (ED) of DR5 to drive its unconventional activation in the Golgi apparatus [1, 2]. Here, using chemical genetics to uncouple stress sensing from ISR activation, we found that DR5 signaling from the Golgi apparatus is integral to the ISR and not specific to ER stress. Furthermore, we show that DR5 activation can be driven solely by increased expression and does not require its ED. These findings indicate that a general ISR kill switch eliminates irreversibly injured cells.

Indexed as

ApoptosisEndoplasmic Reticulum StressReceptors, TNF-Related Apoptosis-Inducing LigandeIF-2 KinaseGolgi ApparatusHumansLigandsSignal TransductioneIF-2 KinaseLigandsReceptors, TNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID39955274
PMCPMC11830069

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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.