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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncoimmunology
2016 ; 5
(12
): e1238543
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Deficiency of the adaptor protein SLy1 results in a natural killer cell
ribosomopathy affecting tumor clearance
#MMPMID28123874
Arefanian S
; Schäll D
; Chang S
; Ghasemi R
; Higashikubo R
; Zheleznyak A
; Guo Y
; Yu J
; Asgharian H
; Li W
; Gelman AE
; Kreisel D
; French AR
; Zaher H
; Plougastel-Douglas B
; Maggi L
; Yokoyama W
; Beer-Hammer S
; Krupnick AS
Oncoimmunology
2016[]; 5
(12
): e1238543
PMID28123874
show ga
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.