Ubiquitination is a widespread post-translational modification integral to all cellular processes. Substrate ubiquitination is catalysed by a multi-enzyme cascade consisting of E1 activating enzymes, E2 conjugating enzymes, and E3 ligase enzymes. The Tripartite Motif (TRIM) family represents the largest family of RING-type E3 ligases in humans. TRIM proteins share a conserved N-terminal domain architecture consisting of a RING domain, one or two B-box domains, and a coiled-coil. TRIMs are generally believed to bind substrates via their variable C-terminal domains and catalyse ubiquitin transfer via their conserved RING domain. TRIM-catalysed ubiquitination does not generally require additional binding partners, however, TRIM28 has been proposed to be activated and targeted to novel substrates via MAGE protein binding. Not much is known about the ubiquitination activity of TRIM28 in the absence of MAGE proteins. This TRIM has predominantly been studied for its role as a transcriptional coregulator. TRIM28 is a member of the class VI TRIM family, and along with family members TRIM24 and TRIM33 possesses a C-terminal PHD and Bromodomain. The PHD-Bromodomain acts as a histone reader, and the class VI TRIMs can be described as unusual as they all have well-described roles in transcriptional modulation which do not appear to require their E3 ligase activity. The work presented in this thesis provides the first comprehensive analysis of the E3 ligase activity of the class VI TRIM proteins. TRIM28, TRIM24, and TRIM33 are revealed to contain inactive and monomeric RING domains. Furthermore, structural analysis of the TRIM28 RING domain reveals a molecular basis for a lack of RING dimerisation and E2 binding.