ArticleInternational journal of cancer2020
The NEDD4-1 E3 ubiquitin ligase: A potential molecular target for bortezomib sensitivity in multiple myeloma.
Article in International journal of cancer, 2020. 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 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- SNU523 Inhibits Pancreatic Cancer through the Dual Suppression of STAT3 and MEK Signaling Pathways.ACS omega · 2026Article
- FAPαAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- CDX2 Promotes Hepatic Specification of hiPSC-derived Endoderm Through the PI3K-Akt-GSK3β Pathway for Improved Therapeutic Efficacy.Stem cell reviews and reports · 2026Article
- Research advancements regarding the relationship between FBXO2 and malignant tumors (Review).Molecular medicine reports · 2025Review
- Regulatory role of E3 ubiquitin ligases in multiple myeloma: from molecular mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Systematic Analysis of E3 Ligase-Related Genes Identified UBE2L3 as a Prognostic Biomarker Associated With Drug Resistance in Acute Myeloid Leukemia.International journal of general medicine · 2025Article
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Ubiquitin ligase NEDD4 promotes the proliferation of hepatocellular carcinoma cells through targeting PCDH17 protein for ubiquitination and degradation.The Journal of biological chemistry · 2024Article
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023Review
- The role of NEDD4 related HECT-type E3 ubiquitin ligases in defective autophagy in cancer cells: molecular mechanisms and therapeutic perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- Environmental control of Pub1 (NEDD4 family E3 ligase) inLife science alliance · 2022Article
- NEDD4 degrades TUSC2 to promote glioblastoma progression.Cancer letters · 2022Article
- The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2022Review
- NEDD4L binds the proteasome and promotes autophagy and bortezomib sensitivity in multiple myeloma.Cell death & disease · 2022Article
- Lycorine suppresses cell growth and invasion via down-regulation of NEDD4 ligase in bladder cancer.American journal of cancer research · 2022Article
- Review
- Research progress in proteasome inhibitor resistance to multiple myeloma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
Corrections and comments
- Erratum issuedErratum.2020
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
E3 ubiquitin ligases primarily determine the substrate specificity of the ubiquitin-proteasome system and play an essential role in the resistance to bortezomib in multiple myeloma (MM). Neural precursor cell-expressed developmentally downregulated gene 4-1 (NEDD4-1, also known as NEDD4) is a founding member of the NEDD4 family of E3 ligases and is involved in the proliferation, migration, invasion and drug sensitivity of cancer cells. In the present study, we investigated the role of NEDD4-1 in MM cells and explored its underlying mechanism. Clinically, low NEDD4-1 expression has been linked to poor prognosis in patients with MM. Functionally, NEDD4-1 knockdown (KD) resulted in bortezomib resistance in MM cells in vitro and in vivo. The overexpression (OE) of NEDD4-1, but not an enzyme-dead NEDD4-1-C867S mutant, had the opposite effect. Furthermore, the overexpression of NEDD4-1 in NEDD4-1 KD cells resensitized the cells to bortezomib in an add-back rescue experiment. Mechanistically, pAkt-Ser473 levels and Akt signaling were elevated and decreased by NEDD4-1 KD and OE, respectively. NEDD4-1 ubiquitinated Akt and targeted pAkt-Ser473 for proteasomal degradation. More importantly, the NEDD4-1 KD-induced upregulation of Akt expression sensitized MM cells to growth inhibition after treatment with an Akt inhibitor. Collectively, our results suggest that high NEDD4-1 levels may be a potential new therapeutic target in MM.
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