ArticleHepatology (Baltimore, Md.)2019
The BRUCE-ATR Signaling Axis Is Required for Accurate DNA Replication and Suppression of Liver Cancer Development.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- BIRC6 prevents GSDME-mediated pyroptosis and promotes cisplatin resistance via a non-canonical UBC domain-dependent steric hindrance.Cell communication and signaling : CCS · 2026Article
- The IAP family member BRUCE/BIRC6: an emerging new player in balancing life and death.Apoptosis : an international journal on programmed cell death · 2026Review
- BRUCE liver-KO enhances MASLD/MASH development in the steatotic PTEN-KO background by impairing mitochondrial metabolism and activating STAT3.Cell death & disease · 2025Article
- Article
- UBE2S: A novel driver of HIF-1alpha-induced metabolic reprogramming in hepatocellular carcinoma: Editorial on "UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL".Clinical and molecular hepatology · 2025Article
- UBE2S promotes glycolysis in hepatocellular carcinoma by enhancing E3 enzyme-independent polyubiquitination of VHL.Clinical and molecular hepatology · 2024Article
- YTHDC1 mThe EMBO journal · 2024Article
- BIRC6 Modulates the Protein Stability of Axin to Regulate the Growth, Stemness, and Resistance of Renal Cancer Cells via the β-Catenin Pathway.ACS omega · 2024Article
- The Mechanism and Prognostic Value of DNA Polymerase δ Subunits in Hepatocellular Carcinoma: Implications for Precision Therapy.International journal of general medicine · 2022Article
- Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma.Frontiers in immunology · 2022Article
- Article
- BIR repeat-containing ubiquitin conjugating enzyme (BRUCE) regulation of β-catenin signaling in the progression of drug-induced hepatic fibrosis and carcinogenesis.World journal of hepatology · 2021Article
- Review
- N-Myristoylation by NMT1 Is POTEE-Dependent to Stimulate Liver TumorigenesisFrontiers in oncology · 2021Article
- [Effect of small interfering RNA-mediated BIRC6 silencing on apoptosis and autophagy of renal cancer 786-O cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- BRUCE preserves genomic stability in the male germline of mice.Cell death and differentiation · 2020Article
- Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE.Journal of biomedical science · 2020Review
- Loss of BRUCE reduces cellular energy level and induces autophagy by driving activation of the AMPK-ULK1 autophagic initiating axis.PloS one · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Replication fork stability during DNA replication is vital for maintenance of genomic stability and suppression of cancer development in mammals. ATR (ataxia-telangiectasia mutated [ATM] and RAD3-related) is a master regulatory kinase that activates the replication stress response to overcome replication barriers. Although many downstream effectors of ATR have been established, the upstream regulators of ATR and the effect of such regulation on liver cancer remain unclear. The ubiquitin conjugase BRUCE (BIR Repeat containing Ubiquitin-Conjugating Enzyme) is a guardian of chromosome integrity and activator of ATM signaling, which promotes DNA double-strand break repair through homologous recombination. Here we demonstrate the functions for BRUCE in ATR activation in vitro and liver tumor suppression in vivo. BRUCE is recruited to induced DNA damage sites. Depletion of BRUCE inhibited multiple ATR-dependent signaling events during replication stress, including activation of ATR itself, phosphorylation of its downstream targets CHK1 and RPA, and the mono-ubiquitination of FANCD2. Consequently, BRUCE deficiency resulted in stalled DNA replication forks and increased firing of new replication origins. The in vivo impact of BRUCE loss on liver tumorigenesis was determined using the hepatocellular carcinoma model induced by genotoxin diethylnitrosamine. Liver-specific knockout of murine Bruce impaired ATR activation and exacerbated inflammation, fibrosis and hepatocellular carcinoma, which exhibited a trabecular architecture, closely resembling human hepatocellular carcinoma (HCC). In humans, the clinical relevance of BRUCE down-regulation in liver disease was found in hepatitis, cirrhosis, and HCC specimens, and deleterious somatic mutations of the Bruce gene was found in human hepatocellular carcinoma in the Cancer Genome Atlas database. Conclusion: These findings establish a BRUCE-ATR signaling axis in accurate DNA replication and suppression of liver cancer in mice and humans and provides a clinically relevant HCC mouse model.
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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.