ArticleThe Journal of biological chemistry2024
Ubiquitin ligase NEDD4 promotes the proliferation of hepatocellular carcinoma cells through targeting PCDH17 protein for ubiquitination and degradation.
Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- PDLIM2 deficiency mediated by PBXIP1 promotes the proliferation of HCC cells through reducing the polyubiquitination and degradation of TRIM27.European journal of medical research · 2025Article
- Integrating multi-omics and experimental techniques to decode ubiquitinated protein modifications in hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- NUP37 accumulation mediated by TRIM28 enhances lipid synthesis to accelerate HCC progression.Oncogene · 2024Article
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
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Abstract
Neural precursor cell expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, is commonly upregulated in human hepatocellular carcinoma (HCC) and functions as an oncogenic factor in the progression of HCC, but the molecular mechanism needs be further explored. In this study, we found that NEDD4 could facilitate the proliferation of HCC cells, which was associated with regulating the ERK signaling. Further investigation showed that protocadherin 17 (PCDH17) was a potential substrate of NEDD4, and restoration of PCDH17 could block the facilitation of ERK signaling and HCC cells proliferation induced by NEDD4 overexpression. Whereafter, we confirmed that NEDD4 interacted with PCDH17 and promoted the Lys33-linked polyubiquitination and degradation of it via the proteasome pathway. Finally, NEDD4 protein level was found to be inversely correlated with that of PCDH17 in human HCC tissues. In conclusion, these results suggest that NEDD4 acts as an E3 ubiquitin ligase for PCDH17 ubiquitination and degradation thereby promoting the proliferation of HCC cells through regulating the ERK signaling, which may provide novel evidence for NEDD4 to be a promising therapeutic target for HCC.
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