ArticleOncogene2021
UFBP1, a key component in ufmylation, enhances drug sensitivity by promoting proteasomal degradation of oxidative stress-response transcription factor Nrf2.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- The sulfonamide anticancer agent indisulam enhances the chemosensitivity of gastric cancer cells by targeting FKBP8.The FEBS journal · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- UFMylation in lipid metabolism disorders-associated diseases.Molecular biology reports · 2026Review
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- UFBP1 Ameliorates Heat Stress-Induced Apoptosis via Mitochondria-Mediated Pathway in Bovine Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2025Article
- The histone demethylase KDM5C enhances the sensitivity of acute myeloid leukemia cells to lenalidomide by stabilizing cereblon.Cellular & molecular biology letters · 2025Article
- The Role of UFMylation in the Development and Progression of Gastric Cancer.Oncology research · 2025Review
- Mithramycin targets head and neck cancer stem cells by inhibiting Sp1 and UFMylation.Cancer cell international · 2024Article
- Lys-63-specific deubiquitinase BRCC36 enhances the sensitivity of multiple myeloma cells to lenalidomide by inhibiting lysosomal degradation of cereblon.Cellular and molecular life sciences : CMLS · 2024Article
- UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.Molecular and cellular biochemistry · 2024Article
- Energy metabolism: a new target for gastric cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Role of UFMylation in tumorigenesis and cancer immunotherapy.Frontiers in immunology · 2024Review
- Encystation and Stress Responses under the Control of Ubiquitin-like Proteins in Pathogenic Amoebae.Microorganisms · 2023Review
- Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress.Cell death & disease · 2023Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- UFMylation System: An Emerging Player in Tumorigenesis.Cancers · 2022Review
- Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development.Molecules and cells · 2022Article
- Naringenin Regulates FKBP4/NR3C1/NRF2 Axis in Autophagy and Proliferation of Breast Cancer and Differentiation and Maturation of Dendritic Cell.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The key component in the UFM1 conjugation system, UFM1-binding and PCI domain-containing protein 1 (UFBP1), regulates many biological processes. Recently it has been shown that low UFBP1 protein level is associated with the worse outcome of gastric cancer patients. However, how it responses to the sensitivity of gastric cancer to chemotherapy drugs and the underlying molecular mechanism remain elusive. Here, we discovered that high UFBP1 expression increases the progression-free survival of advanced gastric cancer patients treated with platinum-based chemotherapy. Cell-line based studies unveiled that UFBP1 expression enhances while UFBP1 knockdown attenuates the sensitivity of gastric cancer cells to cisplatin. High-throughput SILAC-based quantitative proteomic analysis revealed that the protein level of aldo-keto reductase 1Cs (AKR1Cs) is significantly downregulated by UFBP1. Flow cytometry analysis showed that UFBP1 expression increases while UFBP1 knockdown reduces reactive oxygen species upon cisplatin treatment. We further disclosed that UFBP1 attenuates the gene expression of AKR1Cs and the transcription activity of the master oxidative stress-response transcription factor Nrf2 (nuclear factor erythroid-2-related factor 2). Detailed mechanistic studies manifested that UFBP1 promotes the formation of K48-linked polyubiquitin chains on Nrf2 and thus augments its proteasome-mediated degradation. Experiments using genetic depletion and pharmacological activation in vitro and in vivo demonstrated that UFBP1 enhances the sensitivity of gastric cancer cells to cisplatin through the Nrf2/AKR1C axis. Overall, this work discovered a novel prognostic biomarker for gastric cancer patients treated with platinum-based chemotherapy and elucidated the underlying molecular mechanism, which may benefit to future personalized chemotherapy.
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