Tripartite motif family proteins in inflammatory bowel disease: Mechanisms and potential for interventions

Abstract

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal inflammatory disease that poses a heavy burden to the global healthcare system. However, the current paucity of mechanistic understanding of IBD pathogenesis hampers the development of aetiology-directed therapies. Novel therapeutic options based on IBD pathogenesis are urgently needed for attaining better long-term prognosis for IBD patients. The tripartite motif (TRIM) family is a large protein family including more than 70 structurally conservative members, typically characterized by their RBCC structure, which primarily function as E3 ubiquitin ligases in post-translational modification. They have emerged as regulators of a broad range of cellular mechanisms, including proliferation, differentiation, transcription and immune regulation. TRIM family proteins are involved in multiple diseases, such as viral infection, cancer and autoimmune disorders, including inflammatory bowel disease. This review provides a comprehensive perspective on TRIM proteins' involvement in the pathophysiology and progression of IBD, in particular, on intestinal mucosal barriers, gene susceptibility and opportunistic infections, thus providing novel therapeutic targets for this complicated disease. However, the exact mechanisms of TRIM proteins in IBD pathogenesis and IBD-related carcinogenesis are still unknown, and more studies are warranted to explore potential therapeutic targets of TRIM proteins in IBD.

It’s a TRIM-endous view from the top: the varied roles of TRIpartite Motif proteins in brain development and disease

“…TRIM proteins have been linked to the regulation of many cellular functions, including innate immunity, cell-cycle regulation, transcription regulation, and autophagy ( Rajsbaum et al, 2014 ; Hatakeyama, 2017 ). Although TRIM protein functions have been studied across different tissues [e.g., skeletal muscle ( Perera et al, 2012 ), the heart ( Zhang J.-R. et al, 2020 ), and the digestive system ( Chen et al, 2022 )] and in multiple disease settings [e.g., immunity ( Kirmaier et al, 2010 ; Vaysburd et al, 2013 ) and cancer ( Hatakeyama, 2011 , 2017 )], here we will focus on the roles of TRIMs in brain health and disease, which themselves are diverse and extensive, with a multitude of TRIMs implicated across many different brain areas ( Figures 1 , 2 ).…”