ArticlePloS one2016
GADD34 Keeps the mTOR Pathway Inactivated in Endoplasmic Reticulum Stress Related Autophagy.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Fine-Tuning of the Endoplasmic Reticulum Stress Response Mechanism Plays a Key Role in Cellular Survival-A Mathematical Study.International journal of molecular sciences · 2025Article
- Article
- Mechanism of Decision Making between Autophagy and Apoptosis Induction upon Endoplasmic Reticulum Stress.International journal of molecular sciences · 2024Review
- The Dual Role of Sulforaphane-Induced Cellular Stress-A Systems Biological Study.International journal of molecular sciences · 2024Article
- The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).International journal of molecular sciences · 2023Review
- CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns.Cell communication and signaling : CCS · 2023Article
- Role of unfolded protein response and ER-associated degradation under freezing, anoxia, and dehydration stresses in the freeze-tolerant wood frogs.Cell stress & chaperones · 2023Article
- Silencing TUFM Inhibits Development of Monocrotaline-Induced Pulmonary Hypertension by Regulating Mitochondrial Autophagy via AMPK/mTOR Signal Pathway.Oxidative medicine and cellular longevity · 2022Article
- Marchantia polymorpha L. ethanol extract induces apoptosis in hepatocellular carcinoma cells via intrinsic- and endoplasmic reticulum stress-associated pathways.Chinese medicine · 2021Article
- Guanabenz Sensitizes Glioblastoma Cells to Sunitinib by Inhibiting GADD34-Mediated Autophagic Signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Autophagy-dependent survival is controlled with a unique regulatory network upon various cellular stress events.Cell death & disease · 2021Article
- Proteoglycan-driven Autophagy: A Nutrient-independent Mechanism to Control Intracellular Catabolism.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Fine-tuning of AMPK-ULK1-mTORC1 regulatory triangle is crucial for autophagy oscillation.Scientific reports · 2020Article
- GADD34 is a modulator of autophagy during starvation.Science advances · 2020Article
- Endorepellin evokes an angiostatic stress signaling cascade in endothelial cells.The Journal of biological chemistry · 2020Article
- Autophagy Function and Regulation in Kidney Disease.Biomolecules · 2020Review
- Salidroside inhibits the proliferation and migration of gastric carcinoma cells and tumor growthRSC advances · 2019Article
- Epigallocatechin-3-Gallate (EGCG) Promotes Autophagy-Dependent Survival via Influencing the Balance of mTOR-AMPK Pathways upon Endoplasmic Reticulum Stress.Oxidative medicine and cellular longevity · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The balance of protein synthesis and proteolysis (i.e. proteostasis) is maintained by a complex regulatory network in which mTOR (mechanistic target of rapamycin serine/threonine kinase) pathway and unfolded protein response are prominent positive and negative actors. The interplay between the two systems has been revealed; however the mechanistic details of this crosstalk are largely unknown. The aim of the present study was to investigate the elements of crosstalk during endoplasmic reticulum stress and to verify the key role of GADD34 in the connection with the mTOR pathway. Here, we demonstrate that a transient activation of autophagy is present in endoplasmic reticulum stress provoked by thapsigargin or tunicamycin, which is turned into apoptotic cell death. The transient phase can be characterized by the elevation of the autophagic marker LC3II/I, by mTOR inactivation, AMP-activated protein kinase activation and increased GADD34 level. The switch from autophagy to apoptosis is accompanied with the appearance of apoptotic markers, mTOR reactivation, AMP-activated protein kinase inactivation and a decrease in GADD34. Inhibition of autophagy by 3-methyladenine shortens the transient phase, while inhibition of mTOR by rapamycin or resveratrol prolongs it. Inhibition of GADD34 by guanabenz or transfection of the cells with siGADD34 results in down-regulation of autophagy-dependent survival and a quick activation of mTOR, followed by apoptotic cell death. The negative effect of GADD34 inhibition is diminished when guanabenz or siGADD34 treatment is combined with rapamycin or resveratrol addition. These data confirm that GADD34 constitutes a mechanistic link between endoplasmic reticulum stress and mTOR inactivation, therefore promotes cell survival during endoplasmic reticulum stress.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.