ArticleMolecular cell2020
Cancer Cells Employ Nuclear Caspase-8 to Overcome the p53-Dependent G2/M Checkpoint through Cleavage of USP28.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- PANoptosis and Immune Remodeling in the Tumor Microenvironment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- Structure Merging Approach Leads to New Dual Potent and Selective USP25/USP28 Inhibitors.Journal of medicinal chemistry · 2026Article
- A novel feedback loop between DYRK2 and USP28 regulates cancer homeostasis and DNA damage signaling.Cell death and differentiation · 2026Article
- Mechanism Analysis of the Effect of Cordycepin on Colorectal CancerCombinatorial chemistry & high throughput screening · 2026Article
- Review
- Caspase-8 expression and its Src dependent phosphorylation on Tyrosine 380 triggers NRF2 signaling activation in glioblastoma.Cell death and differentiation · 2025Article
- TIPIN coordinates ATM-dependent checkpoint and NF-κB signaling to counteract DNA replication damage from topoisomerase inhibition.Communications biology · 2025Article
- The E3 ubiquitin ligase DTX3L and the deubiquitinase USP28 fine-tune DNA repair through mutual regulation of their protein levels.iScience · 2025Article
- Single-Cell and Bulk RNA Sequencing Highlights Intra-Tumoral Heterogeneity and Malignant Progression Mechanisms in Prostate Cancer.Journal of cellular and molecular medicine · 2025Article
- Evolving role of deubiquitinating enzymes in oral cancer (Review).Oncology letters · 2025Review
- The deubiquitinase USP28 maintains the expression of PPARγ and its inactivation protects mice from diet-induced MASH and hepatocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Multi-Omics Analysis of the Anoikis GeneBiomedicines · 2025Article
- 4-Furanylvinylquinoline derivative as a new scaffold for the design of oxidative stress initiator and glucose transporter inhibitor drugs.Scientific reports · 2024Article
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Structural basis for the bi-specificity of USP25 and USP28 inhibitors.EMBO reports · 2024Article
- Cell death shapes cancer immunity: spotlighting PANoptosis.Journal of experimental & clinical cancer research : CR · 2024Review
- Arginine methylation of caspase-8 controls life/death decisions in extrinsic apoptotic networks.Oncogene · 2024Article
- Caspase 8 deletion causes infection/inflammation-induced bone marrow failure and MDS-like disease in mice.Cell death & disease · 2024Article
- A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study.Nature communications · 2024Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 8 countries.
Funding
Abstract
Cytosolic caspase-8 is a mediator of death receptor signaling. While caspase-8 expression is lost in some tumors, it is increased in others, indicating a conditional pro-survival function of caspase-8 in cancer. Here, we show that tumor cells employ DNA-damage-induced nuclear caspase-8 to override the p53-dependent G2/M cell-cycle checkpoint. Caspase-8 is upregulated and localized to the nucleus in multiple human cancers, correlating with treatment resistance and poor clinical outcome. Depletion of caspase-8 causes G2/M arrest, stabilization of p53, and induction of p53-dependent intrinsic apoptosis in tumor cells. In the nucleus, caspase-8 cleaves and inactivates the ubiquitin-specific peptidase 28 (USP28), preventing USP28 from de-ubiquitinating and stabilizing wild-type p53. This results in de facto p53 protein loss, switching cell fate from apoptosis toward mitosis. In summary, our work identifies a non-canonical role of caspase-8 exploited by cancer cells to override the p53-dependent G2/M cell-cycle checkpoint.
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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.