The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins
The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins
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DOI：
10.1101/gad.1902910
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发表时间：
2010-04-01
影响因子：
10.5
通讯作者：
Rohatgi, Rajat
中科院分区：
文献类型：
--
作者：
Humke, Eric W.;Dorn, Karolin V.;Rohatgi, Rajat
由Hedgehog信号传导协调的转录程序依赖于转录因子的Gli家族。Gli蛋白可以转化为转录激活因子或截短的转录抑制因子。我们发现，Gli 3和融合的抑制剂（Sufu）之间的相互作用调节Gli 3的抑制剂或激活剂形式的形成。在没有信号传导的情况下，腐乳抑制细胞质中的Gli 3，促进其加工成阻遏物。信号传导的起始触发了Sufu与Gli 3的解离。该事件阻止了阻遏物的形成，而是允许Gli 3进入细胞核，在那里它被转化为不稳定的、差异磷酸化的转录激活因子。这个关键的解离事件取决于Kif 3a，初级纤毛功能所需的驱动蛋白马达。我们认为Sufu-Gli 3相互作用是Hedgehog通路中的一个主要控制点，Hedgehog通路在发育和癌症中都起着重要作用。
The transcriptional program orchestrated by Hedgehog signaling depends on the Gli family of transcription factors. Gli proteins can be converted to either transcriptional activators or truncated transcriptional repressors. We show that the interaction between Gli3 and Suppressor of Fused (Sufu) regulates the formation of either repressor or activator forms of Gli3. In the absence of signaling, Sufu restrains Gli3 in the cytoplasm, promoting its processing into a repressor. Initiation of signaling triggers the dissociation of Sufu from Gli3. This event prevents formation of the repressor and instead allows Gli3 to enter the nucleus, where it is converted into a labile, differentially phosphorylated transcriptional activator. This key dissociation event depends on Kif3a, a kinesin motor required for the function of primary cilia. We propose that the Sufu-Gli3 interaction is a major control point in the Hedgehog pathway, a pathway that plays important roles in both development and cancer.