TRIM65
Description
The TRIM65 (tripartite motif containing 65) is a protein-coding gene located on chromosome 17.
TRIM65, also known as Tripartite motif-containing protein 65, is an E3 ubiquitin ligase that plays a role in several processes, including innate immunity, autophagy, and inflammation. It negatively regulates microRNAs (miRNAs) by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both miRNAs and short interfering RNAs. This ubiquitination results in the suppressed expression of miR-138-5p, leading to increased autophagy. Upon enteroviral infection, TRIM65 promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5, leading to an innate signaling cascade. Mechanistically, TRIM65 selectively recognizes MDA5 filaments that occur on double-stranded RNAs. TRIM65 also plays a role in limiting inflammation through different mechanisms. First, TRIM65 promotes 'Lys-48'-mediated ubiquitination of VCAM1, leading to its degradation and limitation of LPS-induced lung inflammation. In addition, TRIM65 negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3, which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages.
TRIM65 is also known as 4732463G12Rik.
