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Ubiquitin and ubiquitin-like modifiers modulate NK cell-mediated recognition and killing of damaged cells

1 Department of Molecular Medicine, “Sapienza” University of Rome, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Viale Regina Elena 291, 00161, Rome, Italy
2 Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

Special Issues: Novel insights in NK cell receptors and their ligands in health and disease

Efficient elimination of transformed and virus-infected cells by natural killer (NK) cells mainly depends on the recognition of “induced self” ligands by activating receptors, including NKG2D and DNAM1. The surface expression of these ligands in stressed or diseased cells results from the integration of transcriptional, post-transcriptional and post-translational mechanisms. Among post-translational mechanisms, recent findings indicate that ubiquitin and ubiquitin-like modifications, namely ubiquitination and SUMOylation, contribute to a very rapid negative regulation of NKG2D and DNAM1 ligand surface expression promoting either ligand degradation or ligand intracellular retention. On the other hand, accumulating evidences demonstrate that NKG2D receptor expression is down-regulated by ubiquitin-dependent endocytosis upon ligand stimulation. In this scenario, the overall consequence of the post-translational modifications of activating NK cell receptors and of their ligands on target cells is to impair effector cell-mediated recognition of damaged cells. Our review summarizes recent findings on the role of post-translational modifications in the modulation of target cell susceptibility to NK cell-mediated killing.
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Keywords NK cells; activating receptors; activating ligands; ubiquitination; SUMOylation

Citation: Rosa Molfetta, Beatrice Zitti, Angela Santoni, Rossella Paolini. Ubiquitin and ubiquitin-like modifiers modulate NK cell-mediated recognition and killing of damaged cells. AIMS Allergy and Immunology, 2017, 1(4): 164-180. doi: 10.3934/Allergy.2017.4.164

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