ArticleThe Journal of biological chemistry2016
NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling.
Article in The Journal of biological chemistry, 2016. 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, 45 citations in OpenAlex.
- NEDD4L knockdown reduced lipid accumulation in non-alcoholic fatty liver disease by promoting the activity of PI3K/AKT signaling pathway.European journal of medical research · 2025Article
- The Role of the PI3K/Akt/mTOR Pathway in Atherosclerosis: Mechanisms, Therapeutic Potential, and Emerging Targeted Treatments.Current atherosclerosis reports · 2025Review
- Post-translational modifications and the reprogramming of tumor metabolism.Discover oncology · 2025Review
- NEDD4 signaling: a new frontier in the diagnosis and treatment of breast and ovarian cancers.Medical oncology (Northwood, London, England) · 2025Review
- Reversal of endocrine resistance via N6AMT1-NEDD4L pathway-mediated p110α degradation.Oncogene · 2025Article
- ZDHHC5 as a central regulator in a palmitoylation-associated prognostic model for lung adenocarcinoma: insights from pan-cancer and experimental analyses.Frontiers in immunology · 2025Article
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- NEDD4L Suppresses Proliferation and Promotes Apoptosis by Ubiquitinating RAC2 Expression and Acts as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2024Article
- NEDD4L is a promoter for angiogenesis and cell proliferation in human umbilical vein endothelial cells.Journal of cellular and molecular medicine · 2024Article
- EGFR-T790M Mutation-Derived Interactome Rerouted EGFR Translocation Contributing to Gefitinib Resistance in Non-Small Cell Lung Cancer.Molecular & cellular proteomics : MCP · 2023Article
- The RNA-binding protein KSRP aggravates malignant progression of clear cell renal cell carcinoma through transcriptional inhibition and post-transcriptional destabilization of the NEDD4L ubiquitin ligase.Journal of biomedical science · 2023Article
- BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3.Cancer science · 2023Article
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
- Stellettin B Sensitizes Glioblastoma to DNA-Damaging Treatments by Suppressing PI3K-Mediated Homologous Recombination Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Emerging roles of the HECT E3 ubiquitin ligases in gastric cancer.Pathology oncology research : POR · 2023Review
- NEDD4L inhibits glycolysis and proliferation of cancer cells in oral squamous cell carcinoma by inducing ENO1 ubiquitination and degradation.Cancer biology & therapy · 2022Article
- Hypoxic glioma-derived extracellular vesicles harboring MicroRNA-10b-5p enhance M2 polarization of macrophages to promote the development of glioma.CNS neuroscience & therapeutics · 2022Article
- Protective role of microRNA-23a/b-3p inhibition against osteoarthritis through Gremlin1-depenent activation of TGF-β/smad signaling in chondrocytesa.Inflammopharmacology · 2022Article
- Article
- Autophagy of the mNature communications · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic PIK3CA (p110α), the catalytic subunit of class IA PI3K, plays a major role in PI3K-related cancer progression. The mechanisms underlying the dynamic regulation of PIK3CA protein levels remain unknown. Here we demonstrated that PIK3CA is regulated by polyubiquitination. We identified NEDD4L as the E3 ligase that catalyzes PIK3CA polyubiquitination, leading to its proteasome-dependent degradation. NEDD4L ubiquitinates both the free and regulatory subunit-bound PIK3CA but does not ubiquitinate the regulatory subunit of PI3K. Overexpression of NEDD4L accelerates the turnover rate of PIK3CA, whereas suppression of NEDD4L results in not only the accumulation of PIK3CA but also a paradoxical decrease of AKT activation. Thus, we propose that NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway.
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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.