IHB OpenIR  > 水生生物分子与细胞生物学研究中心  > 期刊论文
Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling
Liu, Jing-Xia1; Zhang, Dawei1; Xie, Xunwei1; Ouyang, Gang1; Liu, Xing1; Sun, Yonghua2; Xiao, Wuhan1; Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China.
2013-03-01
Source PublicationDEVELOPMENT
ISSN0950-1991
Volume140Issue:5Pages:1067-1078
AbstractEaf 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.; 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.
SubtypeArticle
KeywordEaf1 Eaf2 Wnt Beta-catenin Tumor Suppressor
Department[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
DOI10.1242/dev.086157
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] ; National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] ; National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] ; National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12]
Indexed BySCI
Language英语
WOS Research AreaDevelopmental Biology
WOS SubjectDevelopmental Biology
WOS IDWOS:000314879800015
WOS KeywordELONGATION-FACTOR ELL ; BETA-CATENIN ; ANTERIOR NEUROECTODERM ; EMBRYONIC AXIS ; HEAD INDUCTION ; ZEBRAFISH WNT8 ; C-MYC ; PROTEINS ; PATHWAY ; MOUSE
Funding OrganizationNational Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] ; National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] ; National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] ; National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12]
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19341
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorXiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China.
Affiliation1.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
Recommended Citation
GB/T 7714
Liu, Jing-Xia,Zhang, Dawei,Xie, Xunwei,et al. Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling[J]. DEVELOPMENT,2013,140(5):1067-1078.
APA Liu, Jing-Xia.,Zhang, Dawei.,Xie, Xunwei.,Ouyang, Gang.,Liu, Xing.,...&Xiao, WH .(2013).Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling.DEVELOPMENT,140(5),1067-1078.
MLA Liu, Jing-Xia,et al."Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling".DEVELOPMENT 140.5(2013):1067-1078.
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