α-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1.
α-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1.
复制标题
DOI：
10.1126/scisignal.2001823
复制
发表时间：
2011-05-24
影响因子：
7.3
通讯作者：
Vasioukhin V
中科院分区：
文献类型：
--
作者：
Silvis MR;Kreger BT;Lien WH;Klezovitch O;Rudakova GM;Camargo FD;Lantz DM;Seykora JT;Vasioukhin V
Hippo通路调节细胞增殖的接触抑制，并最终调节多种多细胞生物体中的器官大小。Hippo通路的失活促进转录辅激活因子Yap 1（Hippo通路效应子）的核定位，并可导致癌症。在此，我们发现毛囊干细胞区室中α E-连环蛋白的缺失导致小鼠皮肤鳞状细胞癌的发生。同时缺失α E-连环蛋白和肿瘤抑制基因p53可加速肿瘤形成。siRNA筛选揭示了αE-catenin和Yap 1之间的功能联系。通过与Yap 1相互作用，αE-catenin促进了Yap 1的胞浆定位，而Yap 1在αE-catenin-null细胞中表现出组成性核定位。我们还发现，在人类鳞状细胞癌肿瘤中，α E-连环蛋白丰度与Yap 1激活之间存在负相关性。这些发现将α E-连环蛋白确定为抑制Yap 1活性并将其隔离在细胞质中的肿瘤抑制因子。
The Hippo pathway regulates contact inhibition of cell proliferation and, ultimately, organ size in diverse multicellular organisms. Inactivation of the Hippo pathway promotes nuclear localization of the transcriptional coactivator Yap1, a Hippo pathway effector, and can cause cancer. Here, we show that deletion of αE-catenin in the hair follicle stem cell compartment resulted in the development of skin squamous cell carcinoma in mice. Tumor formation was accelerated by simultaneous deletion of αE-catenin and the tumor suppressor-encoding gene p53. An siRNA screen revealed a functional connection between αE-catenin and Yap1. By interacting with Yap1, αE-catenin promoted its cytoplasmic localization, and Yap1 showed constitutive nuclear localization in αE-catenin-null cells. We also found an inverse correlation between αE-catenin abundance and Yap1 activation in human squamous cell carcinoma tumors. These findings identify αE-catenin as a tumor suppressor that inhibits Yap1 activity and sequesters it in the cytoplasm.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.8
作者：
Neto-Silva, Ricardo M.;de Beco, Simon;Johnston, Laura A.
通讯作者：
Johnston, Laura A.
影响因子：
7.2
作者：
Donehower, Lawrence A.
通讯作者：
Donehower, Lawrence A.
影响因子：
7.2
作者：
Meng, Wenxiang;Takeichi, Masatoshi
通讯作者：
Takeichi, Masatoshi
影响因子：
64.5
作者：
HIRANO, S;KIMOTO, N;TAKEICHI, M
通讯作者：
TAKEICHI, M