Suppressor of Fused Chaperones Gli Proteins To Generate Transcriptional Responses to Sonic Hedgehog Signaling
Suppressor of Fused Chaperones Gli Proteins To Generate Transcriptional Responses to Sonic Hedgehog Signaling
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融合伴侣 Gli 蛋白的抑制剂，可产生对 Sonic Hedgehog 信号的转录反应
DOI：
10.1128/mcb.00421-16
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发表时间：
2016-11
影响因子：
5.3
通讯作者：
Cheng Steven Y.
中科院分区：
文献类型：
--
作者：
Zhang Ziyu;Shen Longyan;Law Kelvin;Zhang Zengdi;Liu Xiaotong;Hua Hu;Li Sanen;Huang Huijie;Yue Shen;Hui Chi-chung;Cheng Steven Y.
细胞对分级Sonic Hedgehog（Shh）形态发生信号的反应由三个Gli基因协调，这三个基因产生转录激活因子和抑制因子。由肿瘤抑制基因Suppressor of fused（Sufu）编码的该途径的重要下游调节物在Gli蛋白的产生、运输和功能中起关键作用，但其机制仍存在争议。在这里，我们表明，Sufu是上调在积极的Shh响应组织，并伴随着Gli激活剂易位到和Gli阻遏物的核。腐乳的初级纤毛，加强Gli激活剂，但不是阻遏物的贩运，被认为是耦合到其核进口。我们已经确定了一个核输出信号（内斯）基序的豆腐并列蛋白激酶A（PKA）和糖原合成酶激酶3（GSK 3）的双重磷酸化位点，并显示豆腐结合染色质与Gli 1和Gli 3。对单个Ptch 1 −/−、Sufu−/−和Ptch 1 −/−; Sufu−/−双突变胚胎中神经管发育的密切比较表明，Sufu对于Shh信号的最大激活至关重要，Shh信号对最腹侧神经元的特化至关重要。这些数据将腐乳定义为Gli调节和功能的各个方面所需的新型分子伴侣。
ABSTRACT Cellular responses to the graded Sonic Hedgehog (Shh) morphogenic signal are orchestrated by three Gli genes that give rise to both transcription activators and repressors. An essential downstream regulator of the pathway, encoded by the tumor suppressor gene Suppressor of fused (Sufu), plays critical roles in the production, trafficking, and function of Gli proteins, but the mechanism remains controversial. Here, we show that Sufu is upregulated in active Shh responding tissues and accompanies Gli activators translocating into and Gli repressors out of the nucleus. Trafficking of Sufu to the primary cilium, potentiated by Gli activators but not repressors, was found to be coupled to its nuclear import. We have identified a nuclear export signal (NES) motif of Sufu in juxtaposition to the protein kinase A (PKA) and glycogen synthase kinase 3 (GSK3) dual phosphorylation sites and show that Sufu binds the chromatin with both Gli1 and Gli3. Close comparison of neural tube development among individual Ptch1−/−, Sufu−/−, and Ptch1−/−; Sufu−/− double mutant embryos indicates that Sufu is critical for the maximal activation of Shh signaling essential to the specification of the most-ventral neurons. These data define Sufu as a novel class of molecular chaperone required for every aspect of Gli regulation and function.
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影响因子：
11.8
作者：
Qing Zhang;Lei Zhang;B. Wang;Chan-Yen Ou;C. Chien;Jin Jiang
通讯作者：
Qing Zhang;Lei Zhang;B. Wang;Chan-Yen Ou;C. Chien;Jin Jiang
影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
7.3
作者：
Falkenstein, Kristin N.;Vokes, Steven A.
通讯作者：
Vokes, Steven A.
影响因子：
4.8
作者：
Hsu, Shu-Hsuan C.;Zhang, Xiaoyun;Alman, Benjamin A.
通讯作者：
Alman, Benjamin A.
影响因子：
30.8
作者：
HUI, CC;JOYNER, AL
通讯作者：
JOYNER, AL