The Role of E3 Ligases in Macrophage-mediated Inflammation
10.16476/j.pibb.2024.0074
- VernacularTitle:E3连接酶在巨噬细胞介导的炎症中的作用
- Author:
Jia-Bei JIN
1
;
Yi-Dong GE
1
;
Xiao-Feng JIN
1
Author Information
1. Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo 315211, China
- Publication Type:Journal Article
- Keywords:
E3 ligases;
macrophage;
NLRs/RLRs/TLRs;
targeted therapies
- From:
Progress in Biochemistry and Biophysics
2024;51(9):2037-2060
- CountryChina
- Language:English
-
Abstract:
Macrophages, existed in almost all organs of the body, are responsible for detecting tissue injury, pathogens, playing a key role in host defense against a variety of invading pathogens triggering inflammatory responses. Emerging evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification, which is responsible for normal immune responses. However, numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation, mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal expression. Notably, E3 ubiquitin ligases, responsible for recognizing the substrates, are key enzymes in the ubiquitin-proteasome system (UPS) composed of ubiquitin (Ub), ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes, E3 ubiquitin ligases, 26S proteasome, and deubiquitinating enzymes. Intriguingly, several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation, including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and the receptor for advanced glycation end products (RAGE). Herein, we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation, as well as the inhibitors and agonists targeting E3 ligases in macrophage-mediated inflammation, providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.
