Sufu recruits GSK3β for efficient processing of Gli3
Sufu recruits GSK3β for efficient processing of Gli3
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DOI：
10.1016/j.bbrc.2009.07.087
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发表时间：
2009-09-25
影响因子：
3.1
通讯作者：
Miki, Hiroaki
中科院分区：
文献类型：
--
作者：
Kise, Yoshiaki;Morinaka, Akifumi;Miki, Hiroaki
Hedgehog（Hh）信号通过抑制哺乳动物融合蛋白抑制子（Sufu）的功能来激活转录因子Gli。在这里，哺乳动物腐乳的一个新的作用是确定的，它介导的Gli 3的磷酸化的GSK 3 β。对于Gli 3加工以产生Hh靶基因的转录阻遏物是必需的。使用Sufu（-/-）小鼠胚胎成纤维细胞和靶向Sufu的siRNA的研究证明了GIB加工需要Sufu。此外，SUN可以结合GSK 3 β以及Gli 3，并介导三分子复合物Gli 3/Sufu/GSK 3 β的形成。因此，腐乳通过GSK 3 β和Gli 3加工刺激Gli 3磷酸化。此外，声波Hh刺激使Sufu/GSK 3 β复合物与Gli 3解离，导致Gli 3加工的阻断。总的来说，腐乳可能作为GSK 3 β募集者，用于Gli 3加工的Hh依赖性调节。这种功能与果蝇中Costa 12的功能非常相似，表明通过进化实现了功能互补。(C)2009 Elsevier Inc. All rights reserved.
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 GSK3 beta. 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 GIB processing. In addition, SUN can bind to GSK3 beta as well as Gli3, and mediates formation of the trimolecular complex Gli3/Sufu/GSK3 beta. Thus, Sufu stimulates Gli3 phosphorylation by GSK3 beta and Gli3 processing. Furthermore, Sonic Hh stimulation dissociates the Sufu/GSK3 beta complex from Gli3, resulting in the blockade of Gli3 processing. Collectively, Sufu presumably functions as a GSK3 beta recruiter for Hh-dependent regulation of Gli3 processing. Such a function is very Similar to that of Costa12 in Drosophila, suggesting a functional complementation through evolution. (C) 2009 Elsevier Inc. All rights reserved.