ArticleJournal of molecular cell biology2023
Cellular gp96 upregulates AFP expression by blocking NR5A2 SUMOylation and ubiquitination in hepatocellular carcinoma.
Article in Journal of molecular cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Nuclear pore complex protein RANBP2 and related SUMOylation in solid malignancies.Genes & diseases · 2025Review
- Comprehensive Analysis of the SUMO-related Signature: Implication for Diagnosis, Prognosis, and Immune Therapeutic Approaches in Cervical Cancer.Biochemical genetics · 2024Article
- Abnormal protein SUMOylation in liver disease: novel target for therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Article
- MRI Radiomics Combined with Clinicopathological Factors for Predicting 3-Year Overall Survival of Hepatocellular Carcinoma After Hepatectomy.Journal of hepatocellular carcinoma · 2024Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Alpha-fetoprotein (AFP) is the most widely used biomarker for the diagnosis of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients have either normal or marginally increased AFP levels in serum, and the underlying mechanisms are not fully understood. In the present study, we provided in vitro and in vivo evidence that heat shock protein gp96 promoted AFP expression at the transcriptional level in HCC. NR5A2 was identified as a key transcription factor for the AFP gene, and its stability was enhanced by gp96. A further mechanistic study by co-immunoprecipitation, GST pull-down, and molecular docking showed gp96 and the SUMO E3 ligase RanBP2 competitively binding to NR5A2 at the sites spanning from aa 507 to aa 539. The binding of gp96 inhibited SUMOylation, ubiquitination, and subsequent degradation of NR5A2. In addition, clinical analysis of HCC patients indicated that gp96 expression in tumors was positively correlated with serum AFP levels. Therefore, our study uncovered a novel mechanism that gp96 regulates the stability of its client proteins by directly affecting their SUMOylation and ubiquitination. These findings will help in designing more accurate AFP-based HCC diagnosis and progression monitoring approaches.
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Registered trials
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