Nek2Aphosphorylates and stabilizes SuFu: anew strategy of Gli2/Hedgehog signaling regulatory mechanism
Nek2Aphosphorylates and stabilizes SuFu: anew strategy of Gli2/Hedgehog signaling regulatory mechanism
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Nek2A磷酸化并稳定SuFu：Gli2/Hedgehog信号调控机制的新策略
DOI：
10.1016/j.cellsig.2016.06.010
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发表时间：
2016
影响因子：
4.8
通讯作者：
Shiwen Luo
中科院分区：
文献类型：
--
作者：
Yao Wang;Yong Li;Guanghui Hu;Xuan Huang;Hai Rao;Tao Liu;Xiangyang Xiong;Quqin Lu;Shiwen Luo
融合抑制因子(SuFu)在Hedgehog(HH)信号通路中对Gli转录因子的调控起着保守的作用。尽管SuFU在HH途径中具有核心重要性，但人们对其调控知之甚少。在这里，我们以人的SuFu为诱饵，进行了基于Gal4的酵母双杂交筛选，并通过谷胱甘肽-S转移酶下拉和免疫共沉淀实验，鉴定了NIMA相关的表达激酶2A(Nek2A)是一种新的SuFu相互作用蛋白。有趣的是，Nek2A被发现至少部分地依赖于它的激酶活性来稳定SuFu，从而触发SuFu蛋白的磷酸化。此外，磷酸化的SuFU抑制Gli2/HH信号的核定位和转录活性。这些发现揭示了哺乳动物SuFu调控的新机制，并为HH信号在发育和人类疾病中的调控提供了新的见解。
Suppressor of Fused (SuFu) plays a conservative role in the regulation of the Gli transcription factors within the Hedgehog (Hh) signaling pathway. Despite the central importance of SuFu in the Hh pathway, little is known about its regulation. Here, we performed a GAL4-based yeast two-hybrid screen using human SuFu as bait, and identified NIMA-related expressed kinase 2A (Nek2A) as a new SuFu-interacting protein, which was also con-firmed by glutathione-S-transferase pull-down and co-immunoprecipitation assays. Intriguingly, Nek2A is found to stabilize SuFu at least partly depending on its kinase activity, thereby triggering phosphorylation of the SuFu protein. Moreover, the phosphorylated SuFu inhibits the nuclear localization and transcriptional activity.of Gli2/Hh signaling. These findings reveal a new mechanism of mammalian SuFu regulation, and offers novel insights into Hh signaling regulation in development and human disease.