ArticleCancer discovery2023
A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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.
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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.
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Who cites it
48 citing papers in PubMed, 78 citations in OpenAlex.
- Validation of next‑generation sequencing‑derived circulating mRNA variants as potential diagnostic tools in hepatocellular carcinoma and cholangiocarcinoma.Oncology reports · 2026Article
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- The IAP family member BRUCE/BIRC6: an emerging new player in balancing life and death.Apoptosis : an international journal on programmed cell death · 2026Review
- UBA6 serves as a prognostic biomarker and promotes tumor progression in pancreatic ductal adenocarcinoma.Translational cancer research · 2026Article
- GABARAPL1 is important for the activation of HRI during eIF2α phosphorylation-dependent stress response to sodium arsenite.Scientific reports · 2026Article
- Rapid loss of viability in acute myeloid leukemia cells upon telomerase inactivation.Blood advances · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6.Nature structural & molecular biology · 2026Article
- USP10 promotes cell proliferation and gemcitabine resistance in pancreatic cancer by the regulation of IGF2BP3-STEAP3.Oncogene · 2026Article
- Modulation of Nudt21 levels reveals dose-dependent roles of alternative polyadenylation in tissue regeneration.Nature communications · 2026Article
- Article
- Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression.Antioxidants (Basel, Switzerland) · 2025Review
- The generation and consequences of N-terminal proteoform diversity.Cell reports · 2025Review
- USP14-mediated metabolic competition impairs CD8+ T cell immunosurveillance in hepatocellular carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting AQP5-mediated arginine deprivation in gastric cancer stem cells restores NK cell anti-tumor immunity.Cell reports. Medicine · 2025Article
- The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities.Clinical reviews in allergy & immunology · 2025Review
- Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.Science (New York, N.Y.) · 2025Article
- TRIM31 triggers colorectal carcinogenesis and progression by maintaining YBX1 protein stability through ubiquitination modification.Cell death & disease · 2025Article
- ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.NPJ precision oncology · 2025Article
- LncRNA BDNF-AS binds to DNMT1 to suppress angiogenesis in glioma by promoting NEDD4L-mediated YAP1 ubiquitination.Molecular and cellular biochemistry · 2025Article
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Authors and funding
23 authors at 1 institution in 1 country.
Funding
Abstract
Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed of UBA6, BIRC6, KCMF1, and UBR4 is required for the survival of a subset of epithelial tumors that exhibit a high degree of aneuploidy. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization of the heme-regulated inhibitor, a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy. SIGNIFICANCE: We describe the identification of a heretofore unrecognized ubiquitin ligase complex that prevents the aberrant activation of the ISR in a subset of cancer cells. This provides a novel insight on the regulation of ISR and exposes a therapeutic opportunity to selectively eliminate these cancer cells. See related commentary Leli and Koumenis, p. 535. This article is highlighted in the In This Issue feature, p. 517.
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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.