Divergence of hedgehog signal transduction mechanism between Drosophila and mammals
Divergence of hedgehog signal transduction mechanism between Drosophila and mammals
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DOI：
10.1016/j.devcel.2005.12.014
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发表时间：
2006-02-01
影响因子：
11.8
通讯作者：
Taipale, J
中科院分区：
文献类型：
--
作者：
Varjosalo, M;Li, SP;Taipale, J
刺猬（Hh）信号通路在从果蝇到人类的物种发育中起着保守的作用。对Hh的反应是由转录因子Cubitus interruptus （Ci；哺乳动物中的GLIs 1-3）介导的，Hh靶基因表达的组成性激活与几种类型的人类癌症有关。在果蝇中，与Hh受体Smoothened （Smo）直接相关的激酶样蛋白Costal2 （Cos2）对于在没有配体的情况下抑制Ci的转录活性至关重要。另一种蛋白，融合抑制蛋白（Su(Fu)），对Ci活性有微弱的负面影响。通过对Cos2同源蛋白Su（Fu）、Smo和Ci/GLI的功能和序列保守性分析，我们发现果蝇和哺乳动物Hh信号传导机制存在分歧，在小鼠细胞中，主要的Cos2样活性缺失，在没有配体的情况下Hh通路的抑制主要依赖Su（Fu）。
The Hedgehog (Hh) signaling pathway has conserved roles in development of species ranging from Drosophila to humans. Responses to Hh are mediated by the transcription factor Cubitus interruptus (Ci; GLIs 1-3 in mammals), and constitutive activation of Hh target gene expression has been linked to several types of human cancer. In Drosophila, the kinesin-like protein Costal2 (Cos2), which associates directly with the Hh receptor component Smoothened (Smo), is essential for suppression of the transcriptional activity of Ci in the absence of ligand. Another protein, Suppressor of Fused (Su(Fu)), exerts a weak negative influence on Ci activity. Based on analysis of functional and sequence conservation of Cos2 orthologs, Su(Fu), Smo, and Ci/GLI proteins, we find here that Drosophila and mammalian Hh signaling mechanisms have diverged, and that, in mouse cells, major Cos2-like activities are absent and the inhibition of the Hh pathway in the absence of ligand critically depends on Su(Fu).