ArticleCell death and differentiation2010
TRAIL-activated stress kinases suppress apoptosis through transcriptional upregulation of MCL-1.
Article in Cell death and differentiation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Tet2 modulates ER stress responses related to β-cell death and autoimmunity in diabetes.iScience · 2026Article
- Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Methionine-SAM metabolism-dependent ubiquinone synthesis is crucial for ROS accumulation in ferroptosis induction.Nature communications · 2024Article
- Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control.Cell death & disease · 2024Article
- TRAIL receptors promote constitutive and inducible IL-8 secretion in non-small cell lung carcinoma.Cell death & disease · 2022Article
- Review
- Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells.Cell death discovery · 2021Article
- Stress Relief Techniques: p38 MAPK Determines the Balance of Cell Cycle and Apoptosis Pathways.Biomolecules · 2021Review
- Article
- UMI-77 primes glioma cells for TRAIL-induced apoptosis by unsequestering Bim and Bak from Mcl-1.Molecular and cellular biochemistry · 2017Article
- Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017Review
- β-Elemene: Mechanistic Studies on Cancer Cell Interaction and Its Chemosensitization Effect.Frontiers in pharmacology · 2017Review
- Characterization of Potent SMAC Mimetics that Sensitize Cancer Cells to TNF Family-Induced Apoptosis.PloS one · 2016Article
- Surviving apoptosis: life-death signaling in single cells.Trends in cell biology · 2015Review
- miR-22 and miR-29a Are Members of the Androgen Receptor Cistrome Modulating LAMC1 and Mcl-1 in Prostate Cancer.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- Modeling dynamics of cell-to-cell variability in TRAIL-induced apoptosis explains fractional killing and predicts reversible resistance.PLoS computational biology · 2014Article
- The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis.Cancer letters · 2013Article
- Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes.Molecular biology of the cell · 2013Article
- Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family.Cell death and differentiation · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potentially useful anticancer agent with exquisite selectivity for cancer cells. Unfortunately, many cancers show or acquire resistance to TRAIL. In this study we report that TRAIL activates a TGF-beta-activated kinase 1 --> mitogen-activated protein kinase (MAPK) kinase 3 (MKK3)/MKK6 --> p38 pathway in prostate cancer cells that transcriptionally upregulates expression of the antiapoptotic BCL-2 family member MCL-1. TRAIL alone triggered robust formation of the 'death-inducing signaling complex' (DISC), activation of the initiator caspase-8, and truncation of the BH3-only protein BID (tBID). Nevertheless, simultaneous disruption of the p38 MAPK pathway was required to suppress MCL-1 expression, thereby allowing tBID to activate the proapoptotic BCL-2 family member BAK and stimulate mitochondrial outer membrane permeabilization (MOMP). Release of the inhibitor-of-apoptosis (IAP) antagonist, Smac/DIABLO, from the intermembrane space was sufficient to promote TRAIL-induced apoptosis, whereas release of cytochrome c and activation of the apoptosome was dispensable. Even after MOMP, however, mitochondrial-generated reactive oxygen species (ROS) activated a secondary signaling pathway, involving c-Jun N-terminal kinases (JNKs), that similarly upregulated MCL-1 expression and partially rescued some cells from death. Thus, stress kinases activated at distinct steps, before and after mitochondrial injury, mediate TRAIL resistance through maintenance of MCL-1 expression.
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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.