Signaling underlining Drosophila wing morphogenesis and epigenetic regulation

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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.