ArticlePLoS biology2010
HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 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
119 citing papers in PubMed, 236 citations in OpenAlex.
- Activation of heat shock response to treat obese subjects with type 2 diabetes: a prospective, frequency-escalating, randomized, open-label, triple-arm trial.Scientific reports · 2016Trial
- Blocking IL-6 trans-signaling mitigates benzalkonium chloride-induced inflammation, oxidative imbalance, ER stress, and barrier disruption in human corneal epithelial cells.Eye and vision (London, England) · 2026Article
- Mammalian-evolved strains of the fungal pathogen Cryptococcus neoformans show adaptation via heritable transcript level differences specific to mouse MHC haplotype.BMC genomics · 2026Article
- mTOR pathway mediates the endoplasmic reticulum stress -apoptosis of CD4+ T cell through inhibiting autophagy flux in sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Acupuncture-induced HSP70 upregulation in neuroprotection: mitochondrial and anti-apoptotic mechanisms.American journal of translational research · 2026Review
- Heat shock proteins function as signaling molecules to mediate neuron-glia communication in C. elegans during aging.Nature neuroscience · 2025Article
- Review
- Hsa-circ-ACSL1 Enhances Apoptosis and Autophagy in Myocarditis Cardiomyocytes Through the miR-7-5p/XBP1 Axis.Anatolian journal of cardiology · 2024Article
- Heat Shock Proteins Function as Signaling Molecules to Mediate Neuron-Glia Communication During Aging.bioRxiv : the preprint server for biology · 2024Article
- Emerging roles of FOXK2 in cancers and metabolic disorders.Frontiers in oncology · 2024Review
- The role of the peripheral system dysfunction in the pathogenesis of sepsis-associated encephalopathy.Frontiers in microbiology · 2024Review
- Nucleoporin downregulation modulates progenitor differentiation independent of nuclear pore numbers.Communications biology · 2023Article
- RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity.BMC cancer · 2023Article
- Enhanced IRE1α Phosphorylation/Oligomerization-Triggered XBP1 Splicing Contributes to Parkin-Mediated Prevention of SH-SY5Y Cell Death under Nitrosative Stress.International journal of molecular sciences · 2023Article
- The protein kinase R modifies gut physiology to limit colitis.Frontiers in immunology · 2023Article
- Cogs in the autophagic machine-equipped to combat dementia-prone neurodegenerative diseases.Frontiers in molecular neuroscience · 2023Review
- Identification and cross-validation of autophagy-related genes in cardioembolic stroke.Frontiers in neurology · 2023Article
- Non-alcoholic fatty liver disease and liver secretome.Archives of pharmacal research · 2022Review
- X-box binding protein 1 as a key modulator in "healing endothelial cells", a novel EC phenotype promoting angiogenesis after MCAO.Cellular & molecular biology letters · 2022Article
- Looking into Endoplasmic Reticulum Stress: The Key to Drug-Resistance of Multiple Myeloma?Cancers · 2022Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.
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.