The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis.
The Eya1 phosphatase promotes Shh signaling during hindbrain development and oncogenesis.
复制标题
DOI：
10.1016/j.devcel.2015.01.033
复制
发表时间：
2015-04-06
影响因子：
11.8
通讯作者：
Segal RA
中科院分区：
文献类型：
--
作者：
Eisner A;Pazyra-Murphy MF;Durresi E;Zhou P;Zhao X;Chadwick EC;Xu PX;Hillman RT;Scott MP;Greenberg ME;Segal RA
Sonic Hedgehog （Shh）信号在发育和肿瘤发生中至关重要，但调节这一途径的机制尚不清楚。虽然蛋白磷酸化明显影响Shh信号，但对控制该途径的磷酸酶知之甚少。在这里，我们对磷组进行了shRNA筛选，并确定了Eya1是Shh信号的正调节因子。我们发现具有催化活性的磷酸酶Eya1与dna结合蛋白Six1合作促进Shh应答的基因诱导，并且Eya1/Six1共同调节Gli转录激活因子。我们发现，在人类耳聋疾病分支-耳-肾综合征中发生突变的Eya1对sh依赖性后脑生长发育至关重要。此外，Eya1还能促进髓母细胞瘤的生长，髓母细胞瘤是一种依赖sh的后脑瘤。总之，这些结果确定了Eya1和Six1是Shh转录网络在正常发育和肿瘤发生中的关键组成部分。
Sonic Hedgehog (Shh) signaling is critical in development and oncogenesis, but the mechanisms regulating this pathway remain unclear. While protein phosphorylation clearly affects Shh signaling, little is known about phosphatases governing the pathway. Here we conducted an shRNA screen of the phosphatome and identified Eya1 as a positive regulator of Shh signaling. We find that the catalytically active phosphatase Eya1 co-operates with the DNA-binding protein Six1 to promote gene induction in response to Shh, and that Eya1/Six1 together regulate Gli transcriptional activators. We show that Eya1, which is mutated in a human deafness disorder, branchio-oto-renal syndrome, is critical for Shh-dependent hindbrain growth and development. Moreover Eya1 drives the growth of medulloblastoma, a Shh-dependent hindbrain tumor. Together, these results identify Eya1 and Six1 as key components of the Shh transcriptional network in normal development and in oncogenesis.
登录
查看更多内容
影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
影响因子：
7.3
作者：
Evangelista, Marie;Lim, Tze Yang;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
影响因子：
4.6
作者：
El-Hashash, Ahmed H. K.;Turcatel, Gianluca;Warburton, David
通讯作者：
Warburton, David
影响因子：
8.8
作者：
Auvergne RM;Sim FJ;Wang S;Chandler-Militello D;Burch J;Al Fanek Y;Davis D;Benraiss A;Walter K;Achanta P;Johnson M;Quinones-Hinojosa A;Natesan S;Ford HL;Goldman SA
通讯作者：
Goldman SA
影响因子：
4.8
作者：
Hochman, Eldar;Castiel, Asher;Izraeli, Shai
通讯作者：
Izraeli, Shai