1. Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance
- Author
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Hosseinali Asgharian, Andrew E. Gelman, Reza Ghasemi, Alexander S. Krupnick, Hani S. Zaher, Yizhan Guo, Jinsheng Yu, Wenjun Li, Ryuji Higashikubo, Daniel Kreisel, Anthony R. French, Sandra Beer-Hammer, Daniel Schäll, Beatrice Plougastel-Douglas, Leonard B. Maggi, Stephanie Chang, Alex Zheleznyak, Wayne M. Yokoyama, and Saeed Arefanian
- Subjects
0301 basic medicine ,natural killer cells ,Lymphokine-activated killer cell ,Ribosomopathy ,Immunosurveillance ,Immunology ,Cell ,Signal transducing adaptor protein ,ribosomopathy ,Biology ,3. Good health ,Natural killer cell ,lung cancer ,03 medical and health sciences ,Interleukin 21 ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cytoplasm ,medicine ,Immunology and Allergy ,Signal transduction ,Original Research - Abstract
Individuals with robust natural killer (NK) cell function incur lower rates of malignancies. To expand our understanding of genetic factors contributing to this phenomenon, we analyzed NK cells from cancer resistant and susceptible strains of mice. We identified a correlation between NK levels of the X-chromosome-located adaptor protein SLy1 and immunologic susceptibility to cancer. Unlike the case for T or B lymphocytes, where SLy1 shuttles between the cytoplasm and nucleus to facilitate signal transduction, in NK cells SLy1 functions as a ribosomal protein and is located solely in the cytoplasm. In its absence, ribosomal instability results in p53-mediated NK cell senescence and decreased clearance of malignancies. NK defects are reversible under inflammatory conditions and viral clearance is not impacted by SLy1 deficiency. Our work defines a previously unappreciated X-linked ribosomopathy that results in a specific and subtle NK cell dysfunction leading to immunologic susceptibility to cancer.
- Published
- 2016
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