EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output
EGFR signaling attenuates Groucho-dependent repression to antagonize Notch transcriptional output
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DOI：
10.1038/ng1486
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发表时间：
2005-01-01
期刊：
影响因子：
30.8
通讯作者：
Paroush, Z
中科院分区：
文献类型：
--
作者：
Hasson, P;Egoz, N;Paroush, Z
信号通路之间的串扰对于复杂多样的转录网络的产生是至关重要的。EGF受体(EGFR)和Notch通路之间的拮抗作用尤其是有很好的文献记载，尽管其潜在的机制尚不清楚。全球辅阻遏子Groucho(Gro)及其转导素样分裂增强子(TLE)哺乳动物同源物通过多种阻遏物介导抑制，包括Notch、Wnt(Wg)和转化生长因子-β(DPP)信号级联的效应物(1-8)。鉴于GRO和EGFR途径的组成部分之间存在遗传相互作用(9)(参考文献2)。9和P.H.等人，未发表的结果)，我们测试了GRO是否处于这条途径和其他途径的十字路口。在这里，我们表明，响应MAPK激活的GRO的磷酸化减弱了其抑制因子的能力，减弱了Notch级联的效应者-分裂增强子蛋白对Gro依赖的转录沉默。因此，Gro是信号通路之间的一个新的连接点，使EGFR信号能够拮抗Notch和其他潜在的Gro依赖通路的转录输出。
Crosstalk between signaling pathways is crucial for the generation of complex and varied transcriptional networks. Antagonism between the EGF-receptor (EGFR) and Notch pathways in particular is well documented, although the underlying mechanism is poorly understood. The global corepressor Groucho (Gro) and its transducin-like Enhancer-of-split (TLE) mammalian homologs mediate repression by a myriad of repressors, including effectors of the Notch, Wnt (Wg) and TGF-beta (Dpp) signaling cascades(1-8). Given that there are genetic interactions between gro and components of the EGFR pathway(9) (ref. 9 and P. H. et al., unpublished results), we tested whether Gro is at a crossroad between this and other pathways. Here we show that phosphorylation of Gro in response to MAPK activation weakens its repressor capacity, attenuating Gro-dependent transcriptional silencing by the Enhancer-of-split proteins, effectors of the Notch cascade. Thus, Gro is a new junction between signaling pathways, enabling EGFR signaling to antagonize transcriptional output by Notch and potentially other Gro-dependent pathways.