The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling
The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling
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DOI：
10.1126/scisignal.2000405
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发表时间：
2009-06-23
影响因子：
7.3
通讯作者：
Hui, Chi-chung
中科院分区：
文献类型：
--
作者：
Cheung, Helen Oi-Lam;Zhang, Xiaoyun;Hui, Chi-chung
从昆虫到人类，Hedgehog（Hh）信号通路在胚胎发育和组织稳态中具有保守的作用。然而，有人认为，缺乏哺乳动物等效的Costal 2（Cos2）的果蝇和哺乳动物Hh信号转导机制之间的分歧。在这里，我们挑战这一观点，显示驱动蛋白Kif7是一个关键的调节Hh信号在小鼠。与Cos2相似，Kif7与Gli转录因子物理相互作用并控制其蛋白水解和稳定性，并且在Hh信号传导中起积极和消极作用。因此，Kif7是哺乳动物Hh信号机制的缺失组分，这意味着果蝇和哺乳动物系统之间的共性比主流观点所暗示的要大。
From insects to humans, the Hedgehog (Hh) signaling pathway has conserved roles in embryonic development and tissue homeostasis. However, it has been suggested that the lack of mammalian equivalents of Costal2 (Cos2) contributes to a divergence between the mechanism of Drosophila and mammalian Hh signal transduction. Here, we challenge this view by showing that the kinesin protein Kif7 is a critical regulator of Hh signaling in mice. Similar to Cos2, Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling. Thus, Kif7 is a missing component of the mammalian Hh signaling machinery, implying a greater commonality between the Drosophila and mammalian system than the prevailing view suggests.