Signaling underlining Drosophila wing morphogenesis and epigenetic regulation

在这项研究中，我们分离了一个突变体tonalli（tna）作为果蝇翅膀形态发生的必需基因。tna也被研究为参与表观遗传调控的三胸组基因之一。Tonalli和脊椎动物同源物TONAS-1和TONAS-2的重要结构特征是存在称为SP-RING的基序。SP-RING是Siz/PIAS家族SUMO-E3连接酶蛋白中的保守基序。四种脊椎动物皮亚斯家族蛋白在蛋白质SUMO修饰和转录调控方面已被广泛研究。在果蝇中存在两种含SP-RING的蛋白，dPIAS/Zimp/Su（var）2- 10和TONALLI（TNA）。TNA参与表观遗传调控，但其与SUMO修饰的关系尚未显示。脊椎动物TONAS和皮亚斯之间的结构比较揭示了两个SP-RING家族之间的明显差异。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。我们还表明，TONAS具有SUMO-E3连接酶活性，并促进SUMO-2/3在体外和培养细胞中与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.