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首页> 外文期刊>Journal of Cellular Physiology >Phosphorylation Regulates Functions of ZEB1 Transcription Factor
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Phosphorylation Regulates Functions of ZEB1 Transcription Factor

机译：ZEB1的磷酸化调节功能转录因子

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ZEB1 transcription factor is important in both development and disease, including many TGF-induced responses, and the epithelial-to-mesenchymal transition (EMT) by which many tumors undergo metastasis. ZEB1 is differentially phosphorylated in different cell types; however the role of phosphorylation in ZEB1 activity is unknown. Luciferase reporter studies and electrophoresis mobility shift assays (EMSA) show that a decrease in phosphorylation of ZEB1 increases both DNA-binding and transcriptional repression of ZEB1 target genes. Functional analysis of ZEB1 phosphorylation site mutants near the second zinc finger domain (termed ZD2) show that increased phosphorylation (due to either PMA plus ionomycin, or IGF-1) can inhibit transcriptional repression by either a ZEB1-ZD2 domain clone, or full-length ZEB1. This approach identifies phosphosites that have a substantial effect regulating the transcriptional and DNA-binding activity of ZEB1. Immunoprecipitation with anti-ZEB1 antibodies followed by western analysis with a phospho-Threonine-Proline-specific antibody indicates that the ERK consensus site at Thr-867 is phosphorylated in ZEB1. In addition to disrupting in vitro DNA-binding measured by EMSA, IGF-1-induced MEK/ERK phosphorylation is sufficient to disrupt nuclear localization of GFP-ZEB1 fusion clones. These data suggest that phosphorylation of ZEB1 integrates TGF signaling with other signaling pathways such as IGF-1. J. Cell. Physiol. 231: 2205-2217, 2016. (c) 2016 Wiley Periodicals, Inc.
机译：ZEB1转录因子在这两方面都是很重要的发展和疾病,包括许多TGF-induced反应,epithelial-to-mesenchymal过渡(EMT)许多肿瘤发生转移。不同在不同的细胞磷酸化类型;ZEB1活动是未知的。研究和电泳迁移率改变分析(EMSA)表明下降的磷酸化ZEB1 dna结合蛋白和增加ZEB1目标基因的转录镇压。ZEB1磷酸化网站的功能分析第二个锌指域附近的突变体(称为ZD2)表明,增加磷酸化(由于PMA + ionomycin,或igf - 1)由一个抑制转录镇压ZEB1-ZD2域克隆或长篇ZEB1。有一个方法识别phosphosites严重影响调节转录和ZEB1 dna结合活性。与anti-ZEB1抗体免疫沉淀反应其次是西方分析phospho-Threonine-Proline-specific抗体表明ERK共识在刺- 867在ZEB1磷酸化。扰乱体外dna结合蛋白以EMSA来衡量,IGF-1-induced MEK / ERK的磷酸化足以破坏核本地化GFP-ZEB1融合克隆。的磷酸化ZEB1 TGF信号集成与其他信号通路如igf - 1。细胞。威利期刊公司。

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