Ubiquitin-specific proteases in inflammatory bowel disease-related signalling pathway regulation

Abstract

The exact pathogenesis of inflammatory bowel disease (IBD), a chronic gastrointestinal inflammatory disease comprising Crohn’s disease and ulcerative colitis, remains unclear. Studies on ubiquitination, which regulates the degradation of inflammation signalling pathway molecules, and deubiquitination have provided novel insights. Targeting the ubiquitin-specific protease (USP) family of deubiquitinases elucidates IBD signalling pathway mechanisms and possibly, IBD therapeutic solutions. Here, we characterised USPs as chief regulators of pro-inflammatory signalling pathways, including nuclear factor-κB and transforming growth factor-β; analysed the relationship between USPs and IBD pathogenesis in terms of genetic susceptibility, intestinal epithelial barrier, immunity, and gut microbiota; and discussed future research prospects.

Ubiquitin‐specific peptidases: Players in bone metabolism

“…The catalytic site is located at the interface between the palm and thumb subdomains, while the finger subdomain is crucial for the interaction with a distal ubiquitin 42 . Most members of the USP family include a core catalytic domain and other N‐ and C‐terminal extensions, and they may be composed of different domains or sequences with specific functions 43 …”

Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases

“…PTMs such as phosphorylation, acetylation, and ubiquitination play critical roles in the pathogenesis and progression of IBD by modulating a variety of signaling pathways involved in its regulation (14,164). CRLs, the largest family of E3 ubiquitin ligases, have been reported to regulate the development of IBD.…”

“…Ubiquitination, one of the important PTM types, regulates the protein stability, activity, subcellular localization, and interactions in key signaling pathways, subsequently influencing the cell cycle, proliferation, apoptosis, autophagy, and inflammation (10)(11)(12)(13). Dysregulation of the ubiquitination of critical proteins could induce excessive immune activation and AIDs (14,15). The modification of proteins by ubiquitin is a reversible process controlled by ubiquitination and de-ubiquitination.…”

Mini-review: Recent advances in post-translational modification site prediction based on deep learning

“…Ubiquitination serves as a fundamental component of the ubiquitin–proteasome system, mediating more than 80% of protein degradation in eukaryotes [92] . Moreover, aberrant ubiquitination is highly related to the progression of aging [93] and many diseases; for example, the dysregulation of ubiquitin–proteasome system may contribute to the occurrence of neurodegenerative conditions [94] and inflammatory bowel diseases [95] . Therefore, the identification of ubiquitination sites is an essential step in exploring various ubiquitination-involved mechanisms.…”