ArticleThe Journal of biological chemistry2013
A soluble fragment of the tumor antigen BCL2-associated athanogene 6 (BAG-6) is essential and sufficient for inhibition of NKp30 receptor-dependent cytotoxicity of natural killer cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 41 citations in OpenAlex.
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- Attenuation of natural killer cell cytotoxicity by interaction between NKp30 of NK cells and dipeptidase 1 of colon cancer cells.Scientific reports · 2025Article
- NKp30: A Key Membrane Molecule in the Fight Against Cancer and Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Research Progress of NK Cells in Glioblastoma Treatment.OncoTargets and therapy · 2025Review
- Senescent Tumoral HLA-E Reshapes Microenvironment through Impairing NK Cell-Dendritic Cell-T Cell Network in Malignant Pleural Effusion from Lung Cancer.International journal of biological sciences · 2025Article
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- Natural Killer Cell-Based Immunotherapy against Glioblastoma.International journal of molecular sciences · 2023Review
- Single-cell analysis of multiple myelomas refines the molecular features of bortezomib treatment responsiveness.Experimental & molecular medicine · 2022Article
- Engineering a natural ligand-based CAR: directed evolution of the stress-receptor NKp30.Cancer immunology, immunotherapy : CII · 2022Article
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- Analysis of shark NCR3 family genes reveals primordial features of vertebrate NKp30.Immunogenetics · 2021Article
- NK Cells in Chronic Lymphocytic Leukemia and Their Therapeutic Implications.International journal of molecular sciences · 2021Review
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- Engineering of chimeric natural killer cell receptors to develop precision adoptive immunotherapies for cancer.Clinical and experimental immunology · 2020Review
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- Exosome-dependent immune surveillance at the metastatic niche requires BAG6 and CBP/p300-dependent acetylation of p53.Theranostics · 2019Article
- The Natural Cytotoxicity Receptors in Health and Disease.Frontiers in immunology · 2019Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunosurveillance of tumor cells depends on NKp30, a major activating receptor of human natural killer (NK) cells. The human BCL2-associated athanogene 6 (BAG-6, also known as BAT3; 1126 amino acids) is a cellular ligand of NKp30. To date, little is known about the molecular details of this receptor ligand system. Within the current study, we have located the binding site of NKp30 to a sequence stretch of 250 amino acids in the C-terminal region of BAG-6 (BAG-6(686-936)). BAG-6(686-936) forms a noncovalent dimer of 57-59 kDa, which is sufficient for high affinity interaction with NKp30 (KD < 100 nM). As our most important finding, BAG-6(686-936) inhibits NKp30-dependent signaling, interferon-γ release, and degranulation of NK cells in the presence of malignantly transformed target cells. Based on these data, we show for the first time that BAG-6(686-936) comprises a subdomain of BAG-6, which is sufficient for receptor docking and inhibition of NKp30-dependent NK cell cytotoxicity as part of a tumor immune escape mechanism. These molecular insights provide an access point to restore tumor immunosurveillance by NK cells and to increase the efficacy of cellular therapies.
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