%0 Journal Article
%T SPOP promotes ubiquitination and degradation of MyD88 to suppress the innate immune response
%A Fei Wang
%A Guiping Zhao
%A Huanxian Cui
%A Jie Wen
%A Jumei Zheng
%A Maiqing Zheng
%A Na Zhang
%A Qiao Wang
%A Qinghe Li
%A Ranran Liu
%J -
%D 2020
%R 10.1371/journal.ppat.1008188
%X As a canonical adaptor for the Toll-like receptor (TLR) family, myeloid differentiation primary response protein 88 (MyD88) has crucial roles in host defense against infection by microbial pathogens, and its dysregulation might induce autoimmune diseases. Here, we demonstrate that the chicken Cullin 3-based ubiquitin ligase adaptor Speckle-type BTB¨CPOZ protein (chSPOP) recognizes the intermediate domain of chicken MyD88 (chMyD88) and degrades it through the proteasome pathway. Knockdown or genetic ablation of chSPOP leads to aberrant elevation of chMyD88 protein. Through this interaction, chSPOP negatively regulates NF-¦ÊB pathway activity and thus the production of IL-1¦Â upon LPS challenge in chicken macrophages. Furthermore, Spop-deficient mice are more susceptible to infection with Salmonella typhimurium. Collectively, these findings demonstrate MyD88 as a bona fide substrate of SPOP and uncover a mechanism by which SPOP regulates MyD88 abundance and disease susceptibility
%K Chickens
%K Immunoprecipitation
%K Toll-like receptors
%K Enzyme-linked immunoassays
%K Ubiquitination
%K Mouse models
%K Macrophages
%K Transcription factors
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008188