ArticleThe Journal of biological chemistry2013
Nuclear BAG6-UBL4A-GET4 complex mediates DNA damage signaling and cell death.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Systematic discovery of UFM1 receptors reveals a regulatory module in DNA repair directing non-homologous end-joining.Nature communications · 2026Article
- UBL4A as a suppressor of intracerebral hemorrhage by binding to MAPK14 and promoting MAPK14 ubiquitination.Genes & genomics · 2026Article
- Supercharging-enhanced nDIA-MS enables global profiling of drug-induced proteome solubility shifts.Nature communications · 2026Article
- Circular SNX25 encoded radioresistance augmenter facilitates DNA damage repair in hepatocellular carcinoma by targeting BAG6-GET4 interaction.Cell death & disease · 2025Article
- Ovarian SUMO-2/3 targets and their differential response to genotoxic stress induced by 7,12-dimethylbenz(a) anthracene exposure in lean and obese female mice†.Biology of reproduction · 2025Article
- GdX inhibits the occurrence and progression of breast cancer by negatively modulating the activity of STAT3.Cancer biology & therapy · 2024Article
- Ubiquitin-like 4A alleviates the progression of intracerebral hemorrhage by regulating oxidative stress and mitochondrial damage.Experimental animals · 2024Article
- Article
- DERL2 (derlin 2) stabilizes BAG6 (BAG cochaperone 6) in chemotherapy resistance of cholangiocarcinoma.Journal of physiology and biochemistry · 2024Article
- Article
- A genome-wide CRISPR/Cas9 screen identifies DNA-PK as a sensitiser toTheranostics · 2023Article
- Article
- Relationship between genetically determined telomere length and glioma risk.Neuro-oncology · 2022Article
- GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein.Cancer science · 2022Article
- An optimized genome-wide, virus-free CRISPR screen for mammalian cells.Cell reports methods · 2021Article
- Plant Mitophagy in Comparison to Mammals: What Is Still Missing?International journal of molecular sciences · 2021Review
- Review
- Mutations in GET4 disrupt the transmembrane domain recognition complex pathway.Journal of inherited metabolic disease · 2020Article
- Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.American journal of human genetics · 2020Article
- Ubl4A is critical for mitochondrial fusion process under nutrient deprivation stress.PloS one · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
BCL2-associated athanogene 6 (BAG6) is a member of the BAG protein family, which is implicated in diverse cellular processes including apoptosis, co-chaperone, and DNA damage response (DDR). Recently, it has been shown that BAG6 forms a stable complex with UBL4A and GET4 and functions in membrane protein targeting and protein quality control. The BAG6 sequence contains a canonical nuclear localization signal and is localized predominantly in the nucleus. However, GET4 and UBL4A are found mainly in cytoplasm. Whether GET4 and UBL4A are also involved in DDR in the context of the BAG6 complex remains unknown. Here, we provide evidence that nuclear BAG6-UBL4A-GET4 complex mediates DDR signaling and damage-induced cell death. BAG6 appears to be the central component for the process, as depletion of BAG6 leads to the loss of both UBL4A and GET4 proteins and resistance to cell killing by DNA-damaging agents. In addition, nuclear localization of BAG6 and phosphorylation of BAG6 by ATM/ATR are also required for cell killing. UBL4A and GET4 translocate to the nucleus upon DNA damage and appear to play redundant roles in cell killing, as depletion of either one has no effect but co-depletion leads to resistance. All three components of the BAG6 complex are required for optimal DDR signaling, as BAG6, and to a lesser extent, GET4 and UBL4A, regulate the recruitment of BRCA1 to sites of DNA damage. Together our results suggest that the nuclear BAG6 complex is an effector in DNA damage response pathway and its phosphorylation and nuclear localization are important determinants for its function.
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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.