Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia.

Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia.
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DOI:
10.1016/j.ydbio.2009.04.009
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发表时间:
2009-06-15
影响因子:
2.7
通讯作者:
Liu, Aimin
Liu, Aimin
中科院分区:
生物学3区
文献类型:
--
作者:
Jia, Jinping;Kolterud, Asa;Zeng, Huiqing;Hoover, Amber;Teglund, Stephan;Toftgard, Rune;Liu, Aimin

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Hedgehog (Hh) 分泌蛋白家族通过 Gli 转录因子调节哺乳动物发育和癌症形成,Gli 转录因子以激活子和阻遏子形式存在。在脊椎动物中,初级纤毛在 Hh 信号转导中发挥着重要作用,并且是 Gli 蛋白激活剂和阻抑剂活性所必需的。在当前的研究中,我们证明小鼠融合抑制剂 (Sufu) 与 Gli 蛋白相互作用,并在没有纤毛的情况下抑制 Gli 激活剂活性。 Smoothened (Smo) 和 Ift88 突变体中 Sufu 的去除分别导致 Hh 信号传导的完全激活,这表明 Smo 介导的 Sufu 抑制,而不是 Sufu 的抑制功能,需要纤毛。最后,我们表明,无论存在还是不存在纤毛,Sufu 对于小鼠中 Gli3 蛋白的适当激活剂/阻抑剂比例都很重要。
The Hedgehog (Hh) family of secreted proteins regulates mammalian development and cancer formation through Gli transcription factors, which exist in both activator and repressor forms. In vertebrates, the primary cilia play an essential role in Hh signal transduction and are required for both the activator and repressor activities of Gli proteins. In the current study, we demonstrate that mouse Suppressor of Fused (Sufu) interacts with Gli proteins and inhibits Gli activator activity in the absence of cilia. Removal of Sufu in both Smoothened (Smo) and Ift88 mutants, respectively, leads to full activation of Hh signaling, suggesting that Smo-mediated repression of Sufu, but not the inhibitory function of Sufu, requires cilia. Finally, we show that Sufu is important for proper activator/repressor ratio of Gli3 protein in mice, both in the presence and absence of cilia.
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