Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Beatrice Zitti, Rosa Molfetta, Cinzia Fionda, Linda Quatrini, Helena Stabile, Mario Lecce, Valeria de Turris, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Marco Cippitelli, Angela Gismondi, Angela Santoni, Rossella Paolini

ABSTRACT

Natural Killer cells are innate lymphocytes involved in tumor immunosurveillance. They express activating receptors able to recognize self-molecules poorly expressed on healthy cells but up-regulated upon stress conditions, including transformation. Regulation of ligand expression in tumor cells mainly relays on transcriptional mechanisms, while the involvement of ubiquitin or ubiquitin-like modifiers remains largely unexplored. Here, we focused on the SUMO pathway and demonstrated that the ligand of DNAM1 activating receptor, PVR, undergoes SUMOylation in multiple myeloma. Concurrently, we found that PVR is preferentially located in intracellular compartments in human multiple myeloma cell lines and malignant plasma cells and that inhibition of the SUMO pathway promotes its translocation to the cell surface, increasing tumor cell susceptibility to NK cell-mediated cytolysis. Our findings provide the first evidence of an innate immune activating ligand regulated by SUMOylation, and confer to this modification a novel role in impairing recognition and killing of tumor cells. More... »

PAGES

10445

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-10403-0

DOI

http://dx.doi.org/10.1038/s41598-017-10403-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091449543

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28874810


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