腐乳招募糖原合成酶激酶3β以高效加工Gli3。
Sufu recruits GSK3beta for efficient processing of Gli3.
作者信息
Kise Yoshiaki, Morinaka Akifumi, Teglund Stephan, Miki Hiroaki
机构信息
Laboratory of Intracellular Signaling, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, Japan.
出版信息
Biochem Biophys Res Commun. 2009 Sep 25;387(3):569-74. doi: 10.1016/j.bbrc.2009.07.087. Epub 2009 Jul 19.
Hedgehog (Hh) signaling activates the transcription factor Gli by suppressing the function of the suppressor of fused (Sufu) protein in mammals. Here, a novel role of mammalian Sufu is identified where it mediates the phosphorylation of Gli3 by GSK3beta, essential for Gli3 processing to generate a transcriptional repressor for Hh-target genes. Studies using Sufu(-/-) mouse embryonic fibroblasts and siRNA targeting Sufu demonstrate the requirement of Sufu for Gli3 processing. In addition, Sufu can bind to GSK3beta as well as Gli3, and mediates formation of the trimolecular complex Gli3/Sufu/GSK3beta. Thus, Sufu stimulates Gli3 phosphorylation by GSK3beta and Gli3 processing. Furthermore, Sonic Hh stimulation dissociates the Sufu/GSK3beta complex from Gli3, resulting in the blockade of Gli3 processing. Collectively, Sufu presumably functions as a GSK3beta recruiter for Hh-dependent regulation of Gli3 processing. Such a function is very similar to that of Costal2 in Drosophila, suggesting a functional complementation through evolution.
在哺乳动物中，刺猬信号通路（Hh）通过抑制融合抑制因子（Sufu）蛋白的功能来激活转录因子Gli。在此，我们发现了哺乳动物Sufu的一个新作用，即它介导GSK3β对Gli3的磷酸化，这对Gli3加工生成Hh靶基因的转录抑制因子至关重要。使用Sufu基因敲除（-/-）小鼠胚胎成纤维细胞和靶向Sufu的小干扰RNA（siRNA）的研究表明，Sufu是Gli3加工所必需的。此外，Sufu能与GSK3β以及Gli3结合，并介导三分子复合物Gli3/Sufu/GSK3β的形成。因此，Sufu促进GSK3β对Gli3的磷酸化以及Gli3的加工。此外，音猬因子（Sonic Hh）刺激会使Sufu/GSK3β复合物与Gli3解离，从而导致Gli3加工受阻。总体而言，Sufu可能作为GSK3β的招募因子参与Hh对Gli3加工的依赖性调控。这种功能与果蝇中的肋骨蛋白2（Costal2）非常相似，表明在进化过程中存在功能互补。
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