ArticleNucleic acids research2015
DDB2 modulates TGF-β signal transduction in human ovarian cancer cells by downregulating NEDD4L.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- The SP1/NEDD4L Axis Suppresses the Breast Cancer Progression by Downregulating SNAI2 Expression.Biochemical genetics · 2026Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- NEDD4 signaling: a new frontier in the diagnosis and treatment of breast and ovarian cancers.Medical oncology (Northwood, London, England) · 2025Review
- Carnitine palmitoyltransferase 1C promotes EMT-associated cisplatin resistance in non-small cell lung cancer cells.Cancer biology & medicine · 2025Article
- LINC01320 facilitates cell proliferation and migration of ovarian cancer via regulating PURB/DDB2/NEDD4L/TGF-β axis.Scientific reports · 2024Article
- DDB2 expression lights the way for precision radiotherapy response in PDAC cells, with or without olaparib.Cell death discovery · 2024Article
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
- A protein with broad functions: damage-specific DNA-binding protein 2.Molecular biology reports · 2022Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- RNA sequencing of glioblastoma tissue slice cultures reveals the effects of treatment at the transcriptional level.FEBS open bio · 2022Article
- DDB2 represses epithelial-to-mesenchymal transition and sensitizes pancreatic ductal adenocarcinoma cells to chemotherapy.Frontiers in oncology · 2022Article
- NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling.Cancer cell international · 2021Article
- ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L.Cell death & disease · 2021Article
- E3 ubiquitin ligase NEDD4L negatively regulates keratinocyte hyperplasia by promoting GP130 degradation.EMBO reports · 2021Article
- Construction of a nine DNA repair-related gene prognostic classifier to predict prognosis in patients with endometrial carcinoma.BMC cancer · 2021Article
- PHLDA1 Modulates the Endoplasmic Reticulum Stress Response and is required for Resistance to Oxidative Stress-induced Cell Death in Human Ovarian Cancer Cells.Journal of Cancer · 2021Article
- Insights Into the Biological Role of NEDD4L E3 Ubiquitin Ligase in Human Cancers.Frontiers in oncology · 2021Review
- Article
- The E2F1 transcription factor and RB tumor suppressor moonlight as DNA repair factors.Cell cycle (Georgetown, Tex.) · 2020Review
- EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair.Oncogene · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The expression of DNA damage-binding protein 2 (DDB2) has been linked to the prognosis of ovarian cancer and its underlying transcription regulatory function was proposed to contribute to the favorable treatment outcome. By applying gene microarray analysis, we discovered neural precursor cell expressed, developmentally downregulated 4-Like (NEDD4L) as a previously unidentified downstream gene regulated by DDB2. Mechanistic investigation demonstrated that DDB2 can bind to the promoter region of NEDD4L and recruit enhancer of zeste homolog 2 histone methyltransferase to repress NEDD4L transcription by enhancing histone H3 lysine 27 trimethylation (H3K27me3) at the NEDD4L promoter. Given that NEDD4L plays an important role in constraining transforming growth factor β signaling by targeting activated Smad2/Smad3 for degradation, we investigated the role of DDB2 in the regulation of TGF-β signaling in ovarian cancer cells. Our data indicate that DDB2 enhances TGF-β signal transduction and increases the responsiveness of ovarian cancer cells to TGF-β-induced growth inhibition. The study has uncovered an unappreciated regulatory mode that hinges on the interaction between DDB2 and NEDD4L in human ovarian cancer cells. The novel mechanism proposes the DDB2-mediated fine-tuning of TGF-β signaling and its downstream effects that impinge upon tumor growth in ovarian cancers.
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