SUMOylation of DLX3 by SUMO1 promotes its transcriptional activity.
SUMOylation of DLX3 by SUMO1 promotes its transcriptional activity.
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SUMO1对DLX3的Sumoylation促进其转录活性。
DOI：
10.1002/jcb.22891
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发表时间：
2011-02
影响因子：
4
通讯作者：
Morasso, Maria I.
中科院分区：
文献类型：
--
作者：
Duverger, Olivier;Chen, Susie X.;Lee, Delia;Li, Tianwei;Chock, P. Boon;Morasso, Maria I.
小泛素样修饰物(SUMO)是以多种方式调节靶蛋白活性的翻译后修饰物。最常见的一组相扑底物是转录因子，其转录活性可以因SUMO化而产生正向或负向的变化。DLX3是一种同源结构域转录因子，参与胎盘发育、毛发、牙齿和指甲等涉及上皮-间充质相互作用的结构的分化以及骨骼的矿化。我们在DLX3的N-末端结构域的K83和K112位置发现了两个潜在的SUMO化位点。在无末端基因家族的6个成员中，DLX3是唯一包含这些位点的成员，这些位点在脊椎动物中高度保守。共表达实验证明，DLX3可以被SUMO1 SUMO化。将赖氨酸83和112定点突变为精氨酸(K83R和K112R)，表明只有K112参与SUMO化。免疫细胞化学分析表明，SUMO化不影响DLX3的亚细胞定位。此外，通过凝胶迁移率改变实验，我们发现DLX3在苏木糖基化后仍能与DNA结合。利用荧光素酶报告基因分析，我们发现DLX3K112R的转录活性明显低于DLX3WT，这表明SUMO化对DLX3的活性有积极的影响。我们发现了DLX3活性的一个新的调控水平，它可能在头发、牙齿和骨骼发育的调控中发挥关键作用。
Small Ubiquitin-Like Modifiers (SUMO) are posttranslational modifiers that regulate target protein activity in diverse ways. The most common group of SUMO substrates is transcription factors, whose transcriptional activity can be altered positively or negatively as a result of SUMOylation. DLX3 is a homeodomain transcription factor involved in placental development, in the differentiation of structures involving epithelial-mesenchymal interactions, such as hair, teeth and nails, and in bone mineralization. We identified two potential SUMOylation sites in the N-terminal domain of DLX3 at positions K83 and K112. Among the six members of the Distal-less family, DLX3 is the only member containing these sites, which are highly conserved among vertebrates. Co-expression experiments demonstrated that DLX3 can be SUMOylated by SUMO1. Site-directed mutagenesis of lysines 83 and 112 to arginines (K83R and K112R) demonstrated that only K112 is involved in SUMOylation. Immunocytochemical analysis showed that SUMOylation does not affect DLX3 subcellular localization. Moreover, using electrophoresis mobility shift assay, we found that DLX3 is still able to bind DNA when SUMOylated. Using luciferase reporter assays, we showed that DLX3K112R exhibits a significantly lower transcriptional activity compared to DLX3WT, suggesting that SUMOylation has a positive effect on DLX3 activity. We identified a new level of regulation in the activity of DLX3 that may play a crucial role in the regulation of hair, teeth and bone development.
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