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2017 ; 40
(4
): 979-986
Nephropedia Template TP
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English Wikipedia
Ubiquitin specific peptidase 4 stabilizes interferon regulatory factor protein
and promotes its function to facilitate interleukin-4 expression in T helper type
2 cells
#MMPMID28791349
Guo Z
; Xu P
; Ge S
; Zhang C
; Zheng X
; Xu J
; Liu Z
; Li B
; Ge S
Int J Mol Med
2017[Oct]; 40
(4
): 979-986
PMID28791349
show ga
We speculated that ubiquitin specific peptidase 4 (USP4) may deubiquitinate
interferon regulatory factor 4 (IRF4) and affect T helper type 2 (Th2) cell
function. This study aimed to validate this hypothesis. Here, the interaction
between USP4 and IRF4 were analyzed by co-immunoprecipitation assay. The
deubiquitin effect of USP4 on IRF4 was analyzed by the Ni-NTA pull down assay.
Luciferase reporter gene constructs were used to analyze the effects of USP4,
IRF4 and nuclear factor of activated T cell-2 (NFATc2) on the activation of the
interleukin-4 (IL-4) promoter. Then, the Th2 cells were infected with sh-USP4 to
analyze the effects of USP4 on the expression levels of IRF4 and Th2-related
cytokines. Western blotting and RT-qPCR were used to detect the protein and mRNA
expression levels, respectively. To determine the levels of IL-4 and IRF4 in
rheumatic heart disease (RHD) patients, peripheral blood mononuclear cells
(PBMCs) were separated by density gradient centrifugation from RHD patients and
healthy controls, and flow cytometric analysis was performed. Our results
validated the interaction between USP4 and IRF4, and effects of USP4 on
stabilization and deubiquitination of IRF4 were also found. Importantly, USP4 and
IRF4 synergized with NFATc2 to specifically enhance NFAT-mediated activation of
the IL-4 promoter. USP4 knockdown not only decreased the expression level of
IRF4, but also affected the expression level of Th2-related cytokines. Finally,
the increased level of IL-4 and IRF4 in PBMCs of RHD patients were observed. On
the whole, our data indicate that USP4 interacts with and deubiquitinates IRF4,
and also stabilizes IRF4 protein and promotes IRF4 function to facilitate IL-4
expression in Th2 cells, which may be related to the pathological process of RHD.