Abstract
BackgroundAxin1 and its homolog Axin2 are scaffold proteins essential for regulating Wnt signaling. Axin-dependent regulation of Wnt is important for various developmental processes and human diseases. However, the involvement of Axin1 and Axin2 in host defense and inflammation remains to be determined.Methods/Principal FindingsHere, we report that Axin1, but not Axin2, plays an essential role in host-pathogen interaction mediated by the Wnt pathway. Pathogenic Salmonella colonization greatly reduces the level of Axin1 in intestinal epithelial cells. This reduction is regulated at the posttranslational level in early onset of the bacterial infection. Further analysis reveals that the DIX domain and Ser614 of Axin1 are necessary for the Salmonella-mediated modulation through ubiquitination and SUMOylation.Conclusion/SignificanceAxin1 apparently has a preventive effect on bacterial invasiveness and inflammatory response during the early stages of infection. The results suggest a distinct biological function of Axin1 and Axin2 in infectious disease and intestinal inflammation while they are functionally equivalent in developmental settings.
Highlights
Axin1 and 2 belong to the Axin family, a negative regulator of the Wnt signaling pathway and a key player in developmental processes and pathogenesis of human diseases [1,2,3,4]
We found that pathogenic Salmonella colonization decreased the Axin1 protein expression in intestinal epithelial cells at the posttranscriptional level
To test if the response is specific to Salmonella, we treated cells with inflammatory cytokine TNF-a, human commensal bacterial E. coli F18, and probiotic strain Lactobacillus rhamnosus GG (Fig. 1B)
Summary
Axin and 2 belong to the Axin family, a negative regulator of the Wnt signaling pathway and a key player in developmental processes and pathogenesis of human diseases [1,2,3,4]. B-catenin levels are kept low through interactions with GSK3b, APC, and Axin [8,9,10,11]. Dishevelled (Dsh) is the upstream regulator of the b-catenin pathway. At the C-terminal end, Axin can bind with Dsh and this interaction reduces b-catenin binding [8,9,10,11]. Axin-dependent regulation of Wnt is important for various developmental processes and human diseases. The involvement of Axin and Axin in host defense and inflammation remains to be determined
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