ArticleJournal of biomedical science2021
NEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway.
Article in Journal of biomedical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Fluorofenidone ameliorates pressure overload-induced heart failure by stabilizing SERCA2a in male mice.Nature communications · 2026Article
- E3 ubiquitin ligase NEDD4 inhibits PEDV infection through ubiquitination and degradation of the viral primase NSP8.Journal of virology · 2026Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- NEDD4 facilitates the progression of endometrial carcinoma by enhancing PAMR1 protein degradation through ubiquitination.Functional & integrative genomics · 2025Article
- Histone lactylation promotes multidrug resistance in hepatocellular carcinoma by forming a positive feedback loop with PTEN.Cell death & disease · 2025Article
- Shikonin blocks CAF-induced TNBC metastasis by suppressing mitochondrial biogenesis through GSK-3β/NEDD4-1 mediated phosphorylation-dependent degradation of PGC-1α.Journal of experimental & clinical cancer research : CR · 2024Article
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 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
- KIR3DL3-HHLA2 and TMIGD2-HHLA2 pathways: The dual role of HHLA2 in immune responses and its potential therapeutic approach for cancer immunotherapy.Journal of advanced research · 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
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- PRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions.iScience · 2022Article
- Human endogenous retrovirus-H long terminal repeat-associating 2: The next immune checkpoint for antitumour therapy.EBioMedicine · 2022Review
- Review
- Extracellular matrix guidance of autophagy: a mechanism regulating cancer growth.Open biology · 2022Review
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe cell adhesion molecule IGPR-1 regulates various critical cellular processes including, cell-cell adhesion, mechanosensing and autophagy and plays important roles in angiogenesis and tumor growth; however, the molecular mechanism governing the cell surface levels of IGPR-1 remains unknown.
resultsIn the present study, we used an in vitro ubiquitination assay and identified ubiquitin E3 ligase NEDD4 and the ubiquitin conjugating enzyme UbcH6 involved in the ubiquitination of IGPR-1. In vitro GST-pulldown and in vivo co-immunoprecipitation assays demonstrated that NEDD4 binds to IGPR-1. Over-expression of wild-type NEDD4 downregulated IGPR-1 and deletion of WW domains (1-4) of NEDD4 revoked its effects on IGPR-1. Knockdown of NEDD4 increased IGPR-1 levels in A375 melanoma cells. Deletion of 57 amino acids encompassing the polyproline rich (PPR) motifs on the C-terminus of IGPR-1 nullified its binding with NEDD4. Furthermore, we demonstrate that NEDD4 promotes K48- and K63-dependent polyubiquitination of IGPR-1. The NEDD4-mediated polyubiquitination of IGPR-1 stimulates lysosomal-dependent degradation of IGPR-1 as the treatment of cells with the lysosomal inhibitors, bafilomycine or ammonium chloride increased IGPR-1 levels ectopically expressed in HEK-293 cells and in multiple endogenously IGPR-1 expressing human skin melanoma cell lines.
conclusionsNEDD4 ubiquitin E3 ligase binds to and mediates polyubiquitination of IGPR-1 leading to its lysosomal-dependent degradation. NEDD4 is a key regulator of IGPR-1 expression with implication in the therapeutic targeting of IGPR-1 in human cancers.
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