Interactions with Costal2 and Suppressor of fused regulate nuclear translocation and activity of Cubitus interruptus
Interactions with Costal2 and Suppressor of fused regulate nuclear translocation and activity of Cubitus interruptus
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DOI：
10.1101/gad.843900
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发表时间：
2000-11-15
影响因子：
10.5
通讯作者：
Jiang, J
中科院分区：
文献类型：
--
作者：
Wang, GL;Amanai, K;Jiang, J
Hedgehog（Hh）家族分泌蛋白控制动物发育中生长和模式化的许多方面。在果蝇中，Hh通过阻止Cubitus interruptus（Ci）的截短阻遏物形式的形成和刺激全长Ci的转录活性来起作用。在这里，我们提供的证据表明，Costal 2（Cos 2）和Suppressor of Fused [Su（fu）]通过将其束缚在细胞质中来抑制Ci，而Hh通过Fused（Eu）诱导Ci的核转位。我们已经确定了一个125个氨基酸的结构域中的C-末端部分的CI介导响应Cos 2抑制。我们发现，Cos 2结合Ci，防止其核进口，并通过这个域抑制其活性。我们还提供了证据表明，苏（fu）通过两种不同的机制来调节Ci：（1）苏（fu）通过Ci的N-末端区域阻断Ci的核输入，（2）通过独立于Ci核转位的机制抑制Ci的活性。最后，我们表明，Cos 2需要转导高水平的Hh信号转导活性，它这样做是通过减轻由苏（fu）施加的Ci活动的阻断。
The Hedgehog (Hh) family of secreted proteins controls many aspects of growth and patterning in animal development. In Drosophila, Hh acts by preventing the formation of a truncated repressor form of Cubitus interruptus (Ci) and stimulating the transcriptional activity of full-length Ci. Here, we provide evidence that Costal2 (Cos2) and Suppressor of Fused [Su(fu)] inhibit Ci by tethering it in the cytoplasm, whereas Hh induces nuclear translocation of Ci through Fused (Eu). We have identified a 125 amino acid domain in the C-terminal part of Ci that mediates response to Cos2 inhibition. We show that Cos2 binds Ci, prevents its nuclear import, and inhibits its activity via this domain. We also provide evidence that Su(fu) regulates Ci through two distinct mechanisms: (1) Su(fu) blocks Ci nuclear import through the N-terminal region of Ci, and (2) it inhibits the activity of Ci through a mechanism independent of Ci nuclear translocation. Finally, we show that Cos2 is required for transducing high levels of Hh signaling activity, and it does so by alleviating the blockage of Ci activity imposed by Su(fu).