The Drosophila STUbL protein Degringolade limits HES functions during embryogenesis
The Drosophila STUbL protein Degringolade limits HES functions during embryogenesis
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DOI：
10.1242/dev.058420
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发表时间：
2011-05-01
期刊：
影响因子：
4.6
通讯作者：
Parkhurst, Susan M.
中科院分区：
文献类型：
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作者：
Barry, Kevin C.;Abed, Mona;Parkhurst, Susan M.
Dgringolade(DGRN)编码果蝇相扑靶向泛素连接酶(STUbL)蛋白，与哺乳动物RNF4类似。DGRN促进HES蛋白毛发的泛素化，这通过抑制其辅因子Groucho的招募来扰乱毛发的抑制活性。我们发现，除Her外，Hey和所有HES家族成员都与Dgrn相互作用，并且是其E3泛素连接酶活性的底物。DGRN表现出动态的亚细胞定位，在HES家族成员活跃的时候聚集在细胞核内，并在性别决定、分割和神经发生过程中限制嘿和HES家族的活动。我们发现Dgrn通过拮抗E(Spl)-C蛋白的活性而与Notch信号通路相互作用。Dgrn零突变体是雌性不育的，产生的胚胎在两到三个核分裂后停止发育。这些突变的胚胎表现出核的碎裂或解聚，并积累了更高水平的相扑结合蛋白，这表明Dgrn在基因组稳定中发挥了作用。
Degringolade (Dgrn) encodes a Drosophila SUMO-targeted ubiquitin ligase (STUbL) protein similar to that of mammalian RNF4. Dgrn facilitates the ubiquitylation of the HES protein Hairy, which disrupts the repressive activity of Hairy by inhibiting the recruitment of its cofactor Groucho. We show that Hey and all HES family members, except Her, interact with Dgrn and are substrates for its E3 ubiquitin ligase activity. Dgrn displays dynamic subcellular localization, accumulates in the nucleus at times when HES family members are active and limits Hey and HES family activity during sex determination, segmentation and neurogenesis. We show that Dgrn interacts with the Notch signaling pathway by it antagonizing the activity of E(spl)-C proteins. dgrn null mutants are female sterile, producing embryos that arrest development after two or three nuclear divisions. These mutant embryos exhibit fragmented or decondensed nuclei and accumulate higher levels of SUMO-conjugated proteins, suggesting a role for Dgrn in genome stability.