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

TRIM蛋白是一个大家族的蛋白质，它们具有共同的基本结构，但在功能和亚细胞定位方面非常多样。它们拥有一个称为RING finger的结构域，该结构域具有“E3泛素连接酶”活性，这意味着它指导称为泛素化的蛋白质修饰过程。泛素化是一种小蛋白质，泛素，与其他蛋白质的连接。据信，它们的泛素连接酶活性对TRIM蛋白的功能至关重要。发现一些TRIM蛋白本身经历另一种称为SUMO化的蛋白质修饰过程。SUMO化还包括小蛋白SUMO与另一种蛋白的连接，并发生在共有位点。SUMO化通常调节修饰蛋白质的细胞内定位、稳定性和/或功能。有趣的是，泛素化和SUMO化是相互依赖的过程。我们实验室的工作表明，一个人类TRIM，特别是TRIM 5 α，具有一个共同的SUMO化位点，调节相邻RING结构域的泛素连接酶活性。计算机搜索SUMO化一致位点表明，大多数人TRIM蛋白含有这样的基序，这意味着SUMO化在该家族蛋白质的功能中起着重要和普遍的作用。

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.