Faculty of Life Sciences, the University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Mol Cell Biol. 2010 May;30(9):2193-205. doi: 10.1128/MCB.01510-09. Epub 2010 Feb 22.
Protein modification by SUMO conjugation has emerged to be an important regulatory event. Recently, the mechanisms through which SUMO elicits its effects on target proteins have been elucidated. One of these is the noncovalent association between SUMO and coregulatory proteins via SUMO interaction motifs (SIMs). We therefore searched for additional binding proteins to elucidate how SUMO acts as a signal to potentiate novel noncovalent interactions with SUMO-binding proteins. We identified an E3 ligase, Pc2, as a SUMO-binding protein with two functionally distinct SIMs. Here, we focus on the role of SIM2 and demonstrate that it is crucial for many of the documented Pc2 functions, which converge on determining its E3 ligase activity. One role of SUMO binding in this context is the subnuclear partitioning of the active form of Ubc9 (SUMO approximately Ubc9) by Pc2. The significance of the SIM2-dependent functions of Pc2 is demonstrated in the control of the precise expression of lineage-specific genes during embryonic stem cell differentiation.
蛋白质的 SUMO 缀合修饰作用已成为一种重要的调控事件。最近，SUMO 对靶蛋白产生影响的机制已经阐明。其中之一是通过 SUMO 相互作用基序 (SIM) ，SUMO 与共调节蛋白的非共价结合。因此，我们搜索了其他结合蛋白，以阐明 SUMO 如何作为信号，增强与 SUMO 结合蛋白的新型非共价相互作用。我们鉴定了一个 E3 连接酶 Pc2 作为具有两个功能不同的 SIM 的 SUMO 结合蛋白。在这里，我们重点关注 SIM2 的作用，并证明它对 Pc2 的许多有文件证明的功能至关重要，这些功能都集中在确定其 E3 连接酶活性上。在这种情况下，SUMO 结合的一个作用是 Pc2 将活性形式的 Ubc9（SUMO 大约 Ubc9）进行亚核分区。Pc2 的 SIM2 依赖性功能的重要性在胚胎干细胞分化过程中对谱系特异性基因的精确表达的控制中得到了证明。
