TRIM28 and TRIM32: multifaceted regulators of innate immunity and antiviral defence.

As versatile E3 ubiquitin ligases, Tripartite Motif (TRIM) proteins are essential elements of the innate immune response. The antiviral roles of TRIM28 and TRIM32 have been well documented, and they function in different ways. TRIM28 regulates the transcriptional expression of antiviral genes, while TRIM32 ubiquitinates host or viral proteins and directs their proteasomal breakdown. When taken together, they represent complementary transcriptional and post-translational host defence mechanisms. While TRIM28 primarily acts as a transcriptional repressor and TRIM32 as an E3 ubiquitin ligase, both proteins also play opposing roles in cell differentiation and immunity. Given the large number of TRIM family members, focusing on these two allows us to present representative transcriptional and ubiquitination-mediated regulatory mechanisms in depth. This review focuses on the regulatory differences in TRIM28 and TRIM32 in RIG-like receptor (RLR) signalling, Stimulator of Interferon Genes (STING) pathways, Toll-like receptor (TLR) signalling, and NOD-like receptors (NLR)-mediated inflammation, which are key to the host's immune response. These protein interactomes exhibit a significant interaction with other cellular pathways, broadening their significance beyond antiviral responses to encompass broader genetic and therapeutic implications.