ArticleCancer science2023
Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency.
Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
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- Disengaging the Engine: Histone Deacetylases 1 and 2-Mediated Acetylation of Hexokinase-2 Regulates Energy Metabolism in Microglia Following Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated regulation of ferroptosis in prostate cancer covering mechanisms, resistance, and translational opportunities.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Demethoxycurcumin suppresses HK2-mediated glycolysis by targeting PTEN/Akt signaling.Cancer gene therapy · 2025Article
- WTAP Mediated m6A Modification Stabilizes PDIA3P1 and Promotes Tumor Progression Driven by Histone Lactylation in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Programmed Cell Death in Cancer.MedComm · 2025Review
- NLRP12 decreases TRIM25-mediated HK2 degradation to promote glycolysis and H3K18la in gastric cancer.Cell death & disease · 2025Article
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- Post-translational modifications and the reprogramming of tumor metabolism.Discover oncology · 2025Review
- The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders.Neuroscience bulletin · 2025Review
- p53 inhibits OTUD5 transcription to promote GPX4 degradation and induce ferroptosis in gastric cancer.Clinical and translational medicine · 2025Article
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- The E3 ligase TRIM7 suppresses the tumorigenesis of gastric cancer by targeting SLC7A11.Scientific reports · 2024Article
- Metabolism-regulated ferroptosis in cancer progression and therapy.Cell death & disease · 2024Review
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency.Cancer science · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), may evolve from the neuroendocrine differentiation (NED) of PCa cells. However, the molecular mechanism that triggers NED is unknown. Trigred motif 36 (TRIM36), a member of the TRIM protein family, exhibits oncogenic or anti-oncogenic roles in various cancers. We have previously reported that TRIM36 is highly expressed to inhibit the invasion and proliferation of PCa. In the present study, we first found that TRIM36 was lowly expressed in NEPC and its overexpression suppressed the NED of PCa. Next, based on proteomic analysis, we found that TRIM36 inhibited the glycolysis pathway through suppressing hexokinase 2 (HK2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate. TRIM36 specifically bound to HK2 through lysine 48 (lys48)-mediated ubiquitination of HK2. Moreover, TRIM36-mediated ubiquitination degradation of HK2 downregulated the level of glutathione peroxidase 4 (GPx4), a process that contributed to ferroptosis. In conclusion, TRIM36 can inhibit glycolysis via lys48-mediated HK2 ubiquitination to reduce GPX4 expression and activate ferroptosis, thereby inhibiting the NED in PCa. Targeting TRIM36 might be a promising approach to retard NED and treat NEPC.
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