Aug 2026· Biomolecules· Vol 16, pp. 1237· 0 citations· 64 references
Medicine
TL;DR
The functional roles of TRIM21 are summarized to provide insights for researchers and inspire further investigation in this area to provide insights for researchers and inspire further investigation in this area.
Abstract
Tripartite motif-containing protein 21 (TRIM21/Ro52) is a pivotal E3 ubiquitin ligase and cytoplasmic fragment crystallizable receptor (FcR). It plays a crucial role in viral infections, autoimmune disorders, and cancers by regulating multiple cell signaling axes, including the NF-κB, RIG-I-like receptor (RLR), cGAS-STING, and Toll-like receptor (TLR) pathways. Type I interferon (IFN-I), a pleiotropic cytokine, is produced via these immune signaling pathways, which are often triggered by viral components. TRIM21 both activates IFN-I signaling and mediates its negative feedback through post-translational modification of key immune signaling proteins, thereby maintaining immune homeostasis. In recent years, TRIM21 has been found to dually regulate autophagy and IFN-I in the context of virus–host interplay. Herein, we systematically summarize the functional roles of TRIM21 in virus-triggered intracellular immunity, aiming to provide insights for researchers and inspire further investigation in this area.
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