TRIMs: selective recruitment at different steps of the NF-κB pathway—determinant of activation or resolution of inflammation

TNF-α-induced NF-κB pathway is an essential component of innate and adaptive immune pathway, and it is tightly regulated by various post-translational modifications including ubiquitination. Oscillations in NF-κB activation and temporal gene expression are emerging as critical determinants of inflammatory response, however, the regulators of unique outcomes in different patho-physiological conditions are not well understood. Tripartite Motif-containing proteins (TRIMs) are RING domain-containing E3 ligases involved in the regulation of cellular homeostasis, metabolism, cell death, inflammation, and host defence. Emerging reports suggest that TRIMs are recruited at different steps of TNF-α-induced NF-κB pathway and modulate via their E3 ligase activity. TRIMs show synergy and antagonism in the regulation of the NF-κB pathway and also regulate it in a feedback manner. TRIMs also regulate pattern recognition receptors (PRRs) mediated inflammatory pathways and may have evolved to directly regulate a specific arm of immune signalling. The review emphasizes TRIM-mediated ubiquitination and modulation of TNF-α-regulated temporal and NF-κB signaling and its possible impact on unique transcriptional and functional outcomes.