Negative Feedback Regulation of Wnt4 Signaling by EAF1 and EAF2/U19
文献类型：期刊论文
| 作者 | Wan, Xiaoyang; Ji, Wei; Mei, Xue; Zhou, Jiangang; Liu, Jing-xia; Fang, Chengchi; Xiao, Wuhan |
| 刊名 | PLOS ONE
 |
| 出版日期 | 2010-02-09 |
| 卷号 | 5期号:2页码:- |
| 关键词 | EXTENSION MOVEMENTS |
| ISSN号 | 1932-6203 |
| 通讯作者 | Wan, XY, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan, Peoples R China |
| 中文摘要 | Previous studies indicated that EAF (ELL-associated factor) family members, EAF1 and EAF2/U19, play a role in cancer and embryogenesis. For example, EAF2/U19 may serve as a tumor suppressor in prostate cancer. At the same time, EAF2/U19 is a downstream factor in the non-canonical Wnt4 signaling pathway required for eye development in Xenopus laevis, and along with EAF1, contributes to convergence and extension movements in zebrafish embryos through Wnt maintenance. Here, we used zebrafish embryos and mammalian cells to show that both EAF1 and EAF2/U19 were up-regulated by Wnt4 (Wnt4a). Furthermore, we found that EAF1 and EAF2/U19 suppressed Wnt4 expression by directly binding to the Wnt4 promoter as seen in chromatin immunoprecipitation assays. These findings indicate that an auto-regulatory negative feedback loop occurs between Wnt4 and the EAF family, which is conserved between zebrafish and mammalian. The rescue experiments in zebrafish embryos showed that early embryonic development required the maintenance of the appropriate levels of Wnt4a through the feedback loop. Others have demonstrated that the tumor suppressors p63, p73 and WT1 positively regulate Wnt4 expression while p21 has the opposite effect, suggesting that maintenance of appropriate Wnt4 expression may also be critical for adult tissue homeostasis and prevention against tumor initiation. Thus, the autoregulatory negative feedback loop that controls expression of Wnt4 and EAF proteins may play an important role in both embryonic development and tumor suppression. Our findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo. |
| 英文摘要 | Previous studies indicated that EAF (ELL-associated factor) family members, EAF1 and EAF2/U19, play a role in cancer and embryogenesis. For example, EAF2/U19 may serve as a tumor suppressor in prostate cancer. At the same time, EAF2/U19 is a downstream factor in the non-canonical Wnt4 signaling pathway required for eye development in Xenopus laevis, and along with EAF1, contributes to convergence and extension movements in zebrafish embryos through Wnt maintenance. Here, we used zebrafish embryos and mammalian cells to show that both EAF1 and EAF2/U19 were up-regulated by Wnt4 (Wnt4a). Furthermore, we found that EAF1 and EAF2/U19 suppressed Wnt4 expression by directly binding to the Wnt4 promoter as seen in chromatin immunoprecipitation assays. These findings indicate that an auto-regulatory negative feedback loop occurs between Wnt4 and the EAF family, which is conserved between zebrafish and mammalian. The rescue experiments in zebrafish embryos showed that early embryonic development required the maintenance of the appropriate levels of Wnt4a through the feedback loop. Others have demonstrated that the tumor suppressors p63, p73 and WT1 positively regulate Wnt4 expression while p21 has the opposite effect, suggesting that maintenance of appropriate Wnt4 expression may also be critical for adult tissue homeostasis and prevention against tumor initiation. Thus, the autoregulatory negative feedback loop that controls expression of Wnt4 and EAF proteins may play an important role in both embryonic development and tumor suppression. Our findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo. |
| WOS标题词 | Science & Technology |
| 学科主题 | Biology; Multidisciplinary Sciences |
| 类目[WOS] | Multidisciplinary Sciences |
| 研究领域[WOS] | Science & Technology - Other Topics |
| 关键词[WOS] | EXTENSION MOVEMENTS ; ELL ; EXPRESSION ; CONVERGENCE ; ACTIVATION ; PROSTATE ; PROTEIN ; GENE |
| 收录类别 | SCI |
| 资助信息 | NSFC [30671037, 30971667, 30700440, 20890113]; National Transgene Project [2009ZX08010-021B]; [2010CB126306]; [2007CB815705]; [2004CB117404] |
| 语种 | 英语 |
| WOS记录号 | WOS:000274442600016 |
| 公开日期 | 2010-12-23 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/13753]  |
| 专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
| 作者单位 | Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wan, Xiaoyang,Ji, Wei,Mei, Xue,et al. Negative Feedback Regulation of Wnt4 Signaling by EAF1 and EAF2/U19[J]. PLOS ONE,2010,5(2):-. |
| APA | Wan, Xiaoyang.,Ji, Wei.,Mei, Xue.,Zhou, Jiangang.,Liu, Jing-xia.,...&Xiao, Wuhan.(2010).Negative Feedback Regulation of Wnt4 Signaling by EAF1 and EAF2/U19.PLOS ONE,5(2),-. |
| MLA | Wan, Xiaoyang,et al."Negative Feedback Regulation of Wnt4 Signaling by EAF1 and EAF2/U19".PLOS ONE 5.2(2010):-. |
入库方式： OAI收割
来源：水生生物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。