N4BP3 facilitates NOD2-MAPK/NF-κB pathway in inflammatory bowel disease through mediating K63-linked RIPK2 ubiquitination.

ABSTRACT: The NOD2 signaling pathway, which plays an important role in the mechanisms of inflammatory bowel disease (IBD) development, has been closely associated with ubiquitination. It was revealed in this study that NOD2 receptor activation could obviously affect the expression of 19 ubiquitination-related genes, with N4BP3 being the most prominently expressed and upregulated. In addition, N4BP3 knockdown was found to reduce the mRNA levels of MDP-induced inflammatory factors, while N4BP3 overexpression elevated their mRNA levels as well as the levels of phospho-ERK1/2, phospho-JNK, phospho-P38 and phospho-NF-κB P65 proteins. Immunoprecipitation tests showed that N4BP3 could pull down RIPK2 and promote its K63-linked ubiquitination. In human tissue specimen assays and mouse experiments, we found

SUBMITTER: Jiang W 

PROVIDER: S-EPMC11487068 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature