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题名: Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling
作者: Liu, Jing-Xia1; Zhang, Dawei1; Xie, Xunwei1; Ouyang, Gang1; Liu, Xing1; Sun, Yonghua2; Xiao, Wuhan1
通讯作者: Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China.
关键词: Eaf1 ; Eaf2 ; Wnt ; beta-catenin ; Tumor suppressor
刊名: DEVELOPMENT
发表日期: 2013-03-01
DOI: 10.1242/dev.086157
卷: 140, 期:5, 页:1067-1078
收录类别: SCI
文章类型: Article
部门归属: [Liu, Jing-Xia; Zhang, Dawei; Xie, Xunwei; Ouyang, Gang; Liu, Xing; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China; [Sun, Yonghua] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12]
类目[WOS]: Developmental Biology
研究领域[WOS]: Developmental Biology
摘要: 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.
英文摘要: 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.
关键词[WOS]: ELONGATION-FACTOR ELL ; BETA-CATENIN ; ANTERIOR NEUROECTODERM ; EMBRYONIC AXIS ; HEAD INDUCTION ; ZEBRAFISH WNT8 ; C-MYC ; PROTEINS ; PATHWAY ; MOUSE
语种: 英语
WOS记录号: WOS:000314879800015
ISSN号: 0950-1991
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/19341
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
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