A Interacting Model: How TRIM21 Orchestrates with Proteins in Intracellular Immunity

Tripartite motif-containing protein 21 (TRIM21), identified as both a cytosolic E3 ubiquitin ligase and FcR (Fragment crystallizable receptor), primarily interacts with proteins via its PRY/SPRY domains and promotes their proteasomal degradation to regulate intracellular immunity. But how TRIM21 involves in intracellular immunity still lacks systematical understanding. Herein, it is probed into the TRIM21-related literature and raises an interacting model about how TRIM21 orchestrates proteins in cytosol. In this novel model, TRIM21 generally interacts with miscellaneous protein in intracellular immunity in two ways: For one, TRIM21 solely plays as an E3, ubiquitylating a glut of proteins that contain specific interferon-regulatory factor, nuclear transcription factor kappaB, virus sensors and others, and involving inflammatory responses. For another, TRIM21 serves as both E3 and specific FcR that detects antibody-complexes and facilitates antibody destroying target proteins. Correspondingly delineated as Fc-independent signaling and Fc-dependent signaling in this review, how TRIM21's interactions contribute to intracellular immunity, expecting to provide a systematical understanding of this important protein and invest enlightenment for further research on the pathogenesis of related diseases and its prospective application is elaborated. TRIM21 interacts with various proteins in different pathways through ubiquitination, significantly related to diseases pathogenesis. Yet there is no clear understanding about TRIM21's complicated interactions in immunity. This review summarizes TRIM21's mechanisms following its unique PRY/SPRY domains. Herein, a novel model -- Fc dependent signaling and Fc independent signaling, is brought out to explain how TRIM21 interacts with different groups the through intracellular immune system. Created with Biorender.com.image