ArticleOncotarget2014
SCF(β-TRCP)-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Inhibiting NEDD4 in triple-negative breast cancer cells reprograms tumor immune microenvironment via the β-TrCP/YAP/ECM axis.Cell reports. Medicine · 2025Article
- Review
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- Review
- FAT10 mediates the sorafenib-resistance of hepatocellular carcinoma cells by stabilizing E3 ligase NEDD4 to enhance PTEN/AKT pathway-induced autophagy.American journal of cancer research · 2024Article
- Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- The HECT family of E3 ubiquitin ligases and PTEN.Seminars in cancer biology · 2022Review
- Environmental control of Pub1 (NEDD4 family E3 ligase) inLife science alliance · 2022Article
- E3 Ubiquitin Ligases: Key Regulators of TGFβ Signaling in Cancer Progression.International journal of molecular sciences · 2021Review
- NEDD4 Induces K48-Linked Degradative Ubiquitination of Hepatitis B Virus X Protein and Inhibits HBV-Associated HCC Progression.Frontiers in oncology · 2021Article
- Exhausted CD4Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Role of Ubiquitination in PTEN Cellular Homeostasis and Its Implications in GB Drug Resistance.Frontiers in oncology · 2020Review
- Review
- Paeoniflorin exhibits antitumor effects in nasopharyngeal carcinoma cells through downregulation of NEDD4.American journal of translational research · 2019Article
- NEDD4 over-expression regulates the afatinib resistant phenotype of NSCLC cells.Oncology signaling · 2018Article
- NEDD4 promotes cell growth and motility in hepatocellular carcinoma.Cell cycle (Georgetown, Tex.) · 2018Article
- Inhibition of NEDD4 inhibits cell growth and invasion and induces cell apoptosis in bladder cancer cells.Cell cycle (Georgetown, Tex.) · 2017Article
- NEDD4 is involved in acquisition of epithelial-mesenchymal transition in cisplatin-resistant nasopharyngeal carcinoma cells.Cell cycle (Georgetown, Tex.) · 2017Article
- The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The HECT domain-containing ubiquitin E3 ligase NEDD4 is widely expressed in mammalian tissues and plays a crucial role in governing a wide spectrum of cellular processes including cell growth, tissue development and homeostasis. Recent reports have indicated that NEDD4 might facilitate tumorigenesis through targeted degradation of multiple tumor suppressor proteins including PTEN. However, the molecular mechanism by which NEDD4 stability is regulated has not been fully elucidated. Here we report that SCF(β-TRCP) governs NEDD4 protein stability by targeting it for ubiquitination and subsequent degradation in a Casein Kinase-I (CKI) phosphorylation-dependent manner. Specifically, depletion of β-TRCP, or inactivation of CKI, stabilized NEDD4, leading to down-regulation of its ubiquitin target PTEN and subsequent activation of the mTOR/Akt oncogenic pathway. Furthermore, we found that CKIδ-mediated phosphorylation of Ser347 and Ser348 on NEDD4 promoted its interaction with SCF(β-TRCP) for subsequent ubiquitination and degradation. As a result, compared to ectopic expression of wild-type NEDD4, introducing a non-degradable NEDD4 (S347A/S348A-NEDD4) promoted cancer cell growth and migration. Hence, our findings revealed the CKI/SCF(β-TRCP) signaling axis as the upstream negative regulator of NEDD4, and further suggested that enhancing NEDD4 degradation, presumably with CKI or SCF(β-TRCP) agonists, could be a promising strategy for treating human cancers.
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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.