Signaling underlining Drosophila wing morphogenesis and epigenetic regulation

在本研究中，我们分离到一个突变型Tonalli(TNA)基因，作为果蝇翅膀形态发生的必需基因。TNA也被认为是参与表观遗传调控的三胸群基因之一。Tonalli和脊椎动物同源物TONAS-1和TONAS-2的显著结构特征是存在一个称为SP环的基序。SP环是SIZ/PIAS家族SUMO-E3连接酶蛋白中的一个保守基序。四种脊椎动物PIAS家族蛋白在蛋白相扑修饰和转录调控方面得到了广泛的研究。果蝇体内含有两种SP环蛋白：dPIAS/Zimp/Su(Var)2-10和Tonalli(TNA)。TNA与表观遗传调控有关，但它与相扑修饰的关系尚未显示。脊椎动物TNASs和PIAS的结构比较表明，这两个SP环家族之间存在明显的差异。在这项研究中，我们发现TONAS蛋白主要定位于细胞核，但也存在于细胞质中。我们还发现TONAS具有SUMO-E3连接酶活性，并在体外和培养细胞中促进SUMO-2/3与TONAS本身的特异性结合。TONAS家族SUMO-E3连接酶的鉴定为剖析脊椎动物细胞中SUMO修饰的调控机制提供了另一种工具。

In this study, we isolated a mutant tonalli (tna) as an essential gene for Drosophila wing morphogenesis. tna also has been studied as one of the Trithorax group genes involved in epigenetic regulation. Significant structural feature of Tonalli and vertebrate homologs, TONAS-1 and TONAS-2 is existence of a motif called SP-RING. SP-RING is a conserved motif among the Siz/PIAS-family SUMO-E3 ligase proteins. Four vertebrate PIAS family proteins have been extensively studied in the context of protein SUMO modification and transcriptional regulation. There are two SP-RING-containing proteins in Drosophila, dPIAS/Zimp/Su(var)2-1 0 and TONALLI (TNA). TNA is implicated in epigenetic regulation, but its relation to SUMO-modification has not been shown. Structural comparison between the vertebrate TONASs and PIAS revealed clear differences between the two SP-RING families. In this study, we showed that TONAS proteins localized predominantly to the nucleus but were also present in the cytoplasm. We also showed that TONAS had SUMO-E3 ligase activity and facilitated the specific conjugation of SUMO-2/3 to TONAS itself in vitro and in cultured cells. The identification of the TONAS family SUMO-E3 ligases provides another tool for dissecting the regulatory mechanism of SUMO modification in vertebrate cells.