期刊
DEVELOPMENT
卷 140, 期 5, 页码 1067-1078出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.086157
关键词
Eaf1; Eaf2; Wnt; beta-catenin; Tumor suppressor
资金
- National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]
- National Transgene Project [2009ZX08010-021B]
- Chinese Academy of Science [KSCX2-EW-Q-12]
Eaf factors play a crucial role in tumor suppression and embryogenesis. To investigate the potential mechanism of Eaf activity, we performed loss-and gain-of-function assays in zebrafish using morpholino and mRNA injections, respectively. We found that eaf1 and eaf2 inhibit Wnt/beta-catenin signaling, thereby modulating mesodermal and neural patterning in the embryo. Moreover, ectopic expression of eaf1 and eaf2 in embryos and cultured cells blocked beta-catenin reporter activity. By immunoprecipitation, we also observed that Eaf1 and Eaf2 bound to the Armadillo repeat region and C-terminus of beta-catenin, as well as to other beta-catenin transcription complex proteins, such as c-Jun, Tcf and Axin, suggesting the formation of a novel complex. In addition, the N-terminus of Eaf1 and Eaf2 bound to beta-catenin and exhibited dominant-negative activity, whereas the C-terminus appeared to either harbor a suppression domain or to recruit a repressor. Both the N- and C-terminus must be intact for Eaf1 and Eaf2 suppressive activity. Lastly, we demonstrate a conservation of biological activities for Eaf family proteins across species. In summary, our evidence points to a novel role for Eaf1 and Eaf2 in inhibiting canonical Wnt/beta-catenin signaling, which might form the mechanistic basis for Eaf1 and Eaf2 tumor suppressor activity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据