PT - JOURNAL ARTICLE AU - Rebecca V Stevens AU - Diego Esposito AU - Katrin Rittinger TI - Characterisation of class VI TRIM RING domains: linking RING activity to C-terminal domain identity AID - 10.26508/lsa.201900295 DP - 2019 Jun 01 TA - Life Science Alliance PG - e201900295 VI - 2 IP - 3 4099 - https://www.life-science-alliance.org/content/2/3/e201900295.short 4100 - https://www.life-science-alliance.org/content/2/3/e201900295.full SO - Life Sci. Alliance2019 Jun 01; 2 AB - TRIM E3 ubiquitin ligases regulate multiple cellular processes, and their dysfunction is linked to disease. They are characterised by a conserved N-terminal tripartite motif comprising a RING, B-box domains, and a coiled-coil region, with C-terminal domains often mediating substrate recruitment. TRIM proteins are grouped into 11 classes based on C-terminal domain identity. Class VI TRIMs, TRIM24, TRIM33, and TRIM28, have been described as transcriptional regulators, a function linked to their C-terminal plant homeodomain and bromodomain, and independent of their ubiquitination activity. It is unclear whether E3 ligase activity is regulated in family members where the C-terminal domains function independently. Here, we provide a detailed biochemical characterisation of the RING domains of class VI TRIMs and describe the solution structure of the TRIM28 RING. Our study reveals a lack of activity of the isolated RING domains, which may be linked to the absence of self-association. We propose that class VI TRIMs exist in an inactive state and require additional regulatory events to stimulate E3 ligase activity, ensuring that associated chromatin-remodelling factors are not injudiciously degraded.