ArticleCell research2021
Neddylation of PTEN regulates its nuclear import and promotes tumor development.
Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 166 citations in OpenAlex.
- Flavokawain A inhibits high glucose-induced malignant progression of lung cancer cells by suppressing PRMT5-mediated PTEN neddylation and nuclear translocation.Oncology letters · 2026Article
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- Role of neddylation in diabetes metabolism: potential therapeutic target.Journal of diabetes and metabolic disorders · 2026Review
- S100A9 lactylation facilitated sepsis-related acute respiratory distress syndrome via promoting transcription activation of IL-1β in macrophages.Cell communication and signaling : CCS · 2026Article
- SIRT1 reduced DDX5 neddylation to attenuate myocardial ischemia/reperfusion injury.Human cell · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Identification of the E3 ligase TRIM21 as a crucial regulator of STAT1 in metabolic dysfunction-associated steatohepatitis.Cell communication and signaling : CCS · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- miR-142-5p promotes TSCM differentiation and suppresses progressive T-cell maturation via targeting PRKCB.Frontiers in immunology · 2026Article
- Mechanism of the enterobacterial metabolite sodium butyrate mediating ferroptosis to affect osteogenic ability of BMSCs in mice with estrogen deficiency-caused osteoporosis via the PTEN/PI3K/AKT pathway.Apoptosis : an international journal on programmed cell death · 2025Article
- Pharmacological induction of acetyl-CoA carboxylase 1 autophagic degradation attenuates lipid accumulation and cholangiocarcinoma progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Bufalin Suppresses Colorectal Cancer Liver Metastasis by Inhibiting De Novo Fatty Acid Synthesis via the PI3K/AKT-Mediated SREBP1/FASN Pathway.Molecules (Basel, Switzerland) · 2025Article
- Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PTEN tumor suppressor opposes the PI3K/Akt signaling pathway in the cytoplasm and maintains chromosomal integrity in the nucleus. Nucleus-cytoplasm shuttling of PTEN is regulated by ubiquitylation, SUMOylation and phosphorylation, and nuclear PTEN has been proposed to exhibit tumor-suppressive functions. Here we show that PTEN is conjugated by Nedd8 under high glucose conditions, which induces PTEN nuclear import without effects on PTEN stability. PTEN neddylation is promoted by the XIAP ligase and removed by the NEDP1 deneddylase. We identify Lys197 and Lys402 as major neddylation sites on PTEN. Neddylated PTEN accumulates predominantly in the nucleus and promotes rather than suppresses cell proliferation and metabolism. The nuclear neddylated PTEN dephosphorylates the fatty acid synthase (FASN) protein, inhibits the TRIM21-mediated ubiquitylation and degradation of FASN, and then promotes de novo fatty acid synthesis. In human breast cancer tissues, neddylated PTEN correlates with tumor progression and poor prognosis. Therefore, we demonstrate a previously unidentified pool of nuclear PTEN in the Nedd8-conjugated form and an unexpected tumor-promoting role of neddylated PTEN.
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