TRIM proteins and the SUMO pathway: a systematic and functional analysis

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TRIM proteins are a large family of proteins that share a common basic structure but are very diverse in their functions and subcellular localization. They harbor a domain called the RING finger which has an “E3 ubiquitin ligase” activity, meaning that it guides the protein modification process known as ubiquitination. Ubiquitination consists in the linkage of a small protein, ubiquitin, to other proteins. It is believed that their ubiquitin ligase activity is central to the function of TRIM proteins. Some TRIM proteins were found to be themselves subjected to another protein modification process known as SUMOylation. SUMOylation also consists in the linkage of a small protein, SUMO, to another protein and occurs at consensus sites. SUMOylation often modulates the intracellular localization, stability and/or function of the modified proteins. Interestingly, ubiquitination and SUMOylation are inter-dependent processes. Work in our laboratory showed that one human TRIM in particular, TRIM5α, harbors a consensus SUMOylation site that modulates the ubiquitin ligase activity of the adjacent RING domain. Computer searches for SUMOylation consensus sites suggested that the majority of human TRIM proteins harbor such motifs, implying that SUMOylation plays an important and general role in the function of proteins of this family.