ArticleThe Journal of biological chemistry2009
Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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Who cites it
64 citing papers in PubMed, 131 citations in OpenAlex.
- Targeted Degradation of Histone Deacetylase 8 Using Proteolysis Targeting Chimeras Technology: A Promising Approach for Glioblastoma Treatment.Drug design, development and therapy · 2026Article
- Role of AMPKZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Dual RNase activity of IRE1 as a target for anticancer therapies.Journal of cell communication and signaling · 2023Review
- A ProbioticToxins · 2023Article
- Identification of novel pathogenic roles of BLZF1/ATF6 in tumorigenesis of gastrointestinal stromal tumor showing Golgi-localized mutant KIT.Cell death and differentiation · 2023Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- The unfolded protein response (UPR) pathway: the unsung hero in breast cancer management.Apoptosis : an international journal on programmed cell death · 2023Review
- Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death.International journal of molecular sciences · 2022Review
- Pharmacological targeting of endoplasmic reticulum stress in disease.Nature reviews. Drug discovery · 2022Review
- Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases.Frontiers in molecular biosciences · 2022Review
- Protein Kinase-Mediated Decision Between the Life and Death.Advances in experimental medicine and biology · 2021Article
- Review
- Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis.International journal of molecular sciences · 2019Review
- Endoplasmic Reticulum Stress and Unfolded Protein Response in Breast Cancer: The Balance between Apoptosis and Autophagy and Its Role in Drug Resistance.International journal of molecular sciences · 2019Review
- Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications.The FEBS journal · 2019Review
- ER Stress Activates the NLRP3 Inflammasome: A Novel Mechanism of Atherosclerosis.Oxidative medicine and cellular longevity · 2019Review
- Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha.Nature communications · 2018Article
- Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice.Scientific reports · 2018Article
- Kaempferol mitigates Endoplasmic Reticulum Stress Induced Cell Death by targeting caspase 3/7.Scientific reports · 2018Article
- Age-related cataracts: Role of unfolded protein response, CaProgress in retinal and eye research · 2017Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) is caused by many disease-relevant conditions, inducing conserved signaling events collectively known as the unfolded protein response. When ER stress is excessive or prolonged, cell death (usually occurring by apoptosis) is triggered. We undertook a chemical biology approach for investigating mechanisms of ER stress-induced cell death. Using a cell-based high throughput screening assay to identify compounds that rescued a neuronal cell line from thapsigargin-induced cell death, we identified benzodiazepinones that selectively inhibit cell death caused by inducers of ER stress (thapsigargin and tunicamycin) but not by inducers of extrinsic (tumor necrosis factor) or intrinsic (mitochondrial) cell death pathways. The compounds displayed activity in several cell lines and primary cultured neurons. Mechanism of action studies revealed that these compounds inhibit ER stress-induced activation of p38 MAPK and kinases responsible for c-Jun phosphorylation. Active benzodiazepinones suppressed cell death at the level of apoptotic signal kinase-1 (ASK1) within the IRE1 pathway but without directly inhibiting the kinase activity of ASK1 or >400 other kinases tested. Rather, active compounds enhanced phosphorylation of serine 967 of ASK1, promoting ASK1 binding to 14-3-3, an event associated with suppression of ASK1 function. Reducing ASK1 protein expression using small interfering RNA also protected cells from ER stress-induced apoptosis, confirming the importance of this protein kinase. Taken together, these findings demonstrate an essential role for ASK1 in cell death induced by ER stress. The compounds identified may prove useful for revealing endogenous mechanisms that regulate inhibitory phosphorylation of ASK1.
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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.