ArticleCell metabolism2019
Deubiquitinases Maintain Protein Homeostasis and Survival of Cancer Cells upon Glutathione Depletion.
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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Who cites it
101 citing papers in PubMed, 193 citations in OpenAlex.
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- Harnessing copper: Innovative approaches to combat neurodegenerative diseases and cancer (Review).International journal of molecular medicine · 2026Review
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- Proteostasis and Its Role in Disease Development.Cell biochemistry and biophysics · 2025Review
- Long noncoding RNA GDIL acts as a scaffold for CHAC1 and XRN2 to promote platinum resistance of colorectal cancer through inhibition of glutathione degradation.Cell death & disease · 2025Article
- Epigenetics disruptions enabled by porphyrin-derived metal-organic frameworks disarm resistances to sonocatalytic ROS anti-tumor actions.Fundamental research · 2025Article
- Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review).Oncology letters · 2024Review
- Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.Science (New York, N.Y.) · 2024Article
- Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.International journal of stem cells · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 1 country.
Funding
Abstract
Cells are subjected to oxidative stress during the initiation and progression of tumors, and this imposes selective pressure for cancer cells to adapt mechanisms to tolerate these conditions. Here, we examined the dependency of cancer cells on glutathione (GSH), the most abundant cellular antioxidant. While cancer cell lines displayed a broad range of sensitivities to inhibition of GSH synthesis, the majority were resistant to GSH depletion. To identify cellular pathways required for this resistance, we carried out genetic and pharmacologic screens. Both approaches revealed that inhibition of deubiquitinating enzymes (DUBs) sensitizes cancer cells to GSH depletion. Inhibition of GSH synthesis, in combination with DUB inhibition, led to an accumulation of polyubiquitinated proteins, induction of proteotoxic stress, and cell death. These results indicate that depletion of GSH renders cancer cells dependent on DUB activity to maintain protein homeostasis and cell viability and reveal a potentially exploitable vulnerability for cancer therapy.
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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.