The development of inflammation is mutually affected with damaged DNA and the abnormal expression of protein modification. Ubiquitination, a way of protein modification, plays a key role in regulating various biological functions including inflammation responses. The ubiquitin enzymes and deubiquitinating enzymes (DUBs) jointly control the ubiquitination. The fact that various ubiquitin linkage chains control the fate of the substrate suggests that the regulatory mechanisms of ubiquitin enzymes are central for ubiquitination. In inflammation diseases, the pro-inflammatory transcription factor NF-κB regulates transcription of pro-labour mediators in response to inflammatory stimuli and expression of numerous genes that control inflammation which is associated with ubiquitination. The ubiquitination regulates NF-κB signaling pathway with many receptor families, including NOD-like receptors (NLR), Toll-like receptors (TLR) and RIG-I-like receptors (RLR), mainly by K63-linked polyubiquitin chains. In this review, we highlight the study of ubiquitination in the inflammatory signaling pathway including NF-κB signaling regulated by ubiquitin enzymes and DUBs. Furthermore, it is emphasized that the interaction of ubiquitin-mediated inflammatory signaling system accurately regulates the inflammatory responses.
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