ArticleCell death & disease2022
UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Clinicopathological significance of AKT and phosphorylated AKT expression in hepatocellular carcinoma: A Meta-Analysis.BMC cancer · 2025Pooled it
- DHODH inhibition drives albumin-mediated drug resistance through TERF2IP lactylation-activated macropinosome-mitochondria contact.Nature communications · 2026Article
- UBE2T-Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation-Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of UBE2T as a novel diagnostic biomarker of psoriasis and proliferating UBE2T+ Keratinocyte in psoriasis.Journal of translational medicine · 2026Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- Autophagy activation by the Becn1Brain, behavior, and immunity · 2026Article
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- The UBE2/E2 ubiquitin-conjugating enzyme family at the interface of tumor biology and antitumor immunity: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Integrative analysis of scRNA-seq and RNA-seq to investigate the prognostic value of lactylation and fibroblast-related genes in intrahepatic cholangiocarcinoma.Scientific reports · 2025Article
- Article
- The deubiquitylase OTUB1 drives gemcitabine resistance in pancreatic cancer by enhancing pyrimidine metabolism through modulating DHODH mRNA stability.Cell death & disease · 2025Article
- ASS1 inhibits liver cancer by promoting CAD ubiquitination and reversing the urea cycle and pyrimidine synthesis imbalance.Hepatology communications · 2025Article
- Landscape analysis of m5C modification regulators unveils DNMT1-mediated dysregulated pyrimidine metabolism in hepatocellular carcinoma.Clinical epigenetics · 2025Article
- UBE2T is a diagnostic and prognostic biomarker for endometrial cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Transcriptomic analysis of the anti-tumor effects of leflunomide in prolactinoma.Scientific reports · 2025Article
- Article
- Identification of prognosis-related key genes in hepatocellular carcinoma based on bioinformatics analysis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- KRASCell reports. Medicine · 2025Article
- Unraveling the Role of Ubiquitin-Conjugating Enzyme UBE2T in Tumorigenesis: A Comprehensive Review.Cells · 2024Review
- Employing a synergistic bioinformatics and machine learning framework to elucidate biomarkers associating asthma with pyrimidine metabolism genes.Respiratory research · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The oncogene protein ubiquitin-conjugating enzyme E2T (UBE2T) is reported to be upregulated in hepatocellular carcinoma (HCC) and correlated with poor clinical outcomes of HCC patients. However, the underlying mechanism by which UBE2T exerts its oncogenic function in HCC remains largely unexplored. In this study, in vitro and in vivo experiments suggested that UBE2T promoted HCC development including proliferation and metastasis. GSEA analysis indicated that UBE2T was positively correlated with pyrimidine metabolism, and LC/MS-MS metabolomics profiling revealed that the key products of pyrimidine metabolism were significantly increased in UBE2T-overexpressing cells. UBE2T overexpression led to the upregulation of several key enzymes catalyzing de novo pyrimidine synthesis, including CAD, DHODH, and UMPS. Moreover, the utilization of leflunomide, a clinically approved DHODH inhibitor, blocked the effect of UBE2T in promoting HCC progression. Mechanistically, UBE2T increased Akt K63-mediated ubiquitination and Akt/β-catenin signaling pathway activation. The disruption of UBE2T-mediated ubiquitination on Akt, including E2-enzyme-deficient mutation (C86A) of UBE2T and ubiquitination-site-deficient mutation (K8/14 R) of Akt impaired UBE2T's effect in upregulating CAD, DHODH, and UMPS. Importantly, we demonstrated that UBE2T was positively correlated with p-Akt, β-catenin, CAD, DHODH, and UMPS in HCC tumor tissues. In summary, our study indicates that UBE2T increases pyrimidine metabolism by promoting Akt K63-linked ubiquitination, thus contributing to HCC development. This work provides a novel insight into HCC development and a potential therapeutic strategy for HCC patients.
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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.