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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >Transcriptional factors Eaf1/2 inhibit endoderm and mesoderm formation via suppressing TGF-beta signaling
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Transcriptional factors Eaf1/2 inhibit endoderm and mesoderm formation via suppressing TGF-beta signaling

机译：转录因子EAF1 / 2通过抑制TGF-β信号传导抑制内胚层和中胚层形成

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摘要

Eaf family genes act in multiple cellular responses such as tumor suppression and embryonic development. In our previous work, Eaf1/2 was found to modulate convergence and extension (C & E) movements and pattern the embryonic anterior-posterior axis during zebrafish embryogenesis. Here, we found that loss-of-function of eaf1/2 caused expanded mesoderm and endoderm in zebrafish embryos and led to the recovery of endoderm specification in TGF-beta factor-mzoep(tz257) mutants, while gain-of-function of eaf1/2 induced reduced mesoderm and endoderm. Analyses of gene expression profiles in Eaf deleted or over-expressed mammalian cells indicated that the roles of Eaf1 and Eaf2 in inhibiting TGF-beta signals were conserved from fish to mammals. By taking advantages of TGF-beta reporters, eaf1/2-fused engrailed proteins, and P53(M214K) mutant, we revealed that Eaf1 and Eaf2 might suppress TGF-beta transduction by synergistically inhibiting none-P53 and P53-required TGF-beta signaling. Furthermore, Eaf1/2 might co-localize and interact with TGF-beta transcriptional factors in the transcriptional complex as repressors to target and suppress TGF-beta signaling activity. Our study unveiled a previously unrecognized link of Eaf1/2 genes with TGF-beta and P53 in vertebrates and demonstrated a conservation of TGF-beta suppression activity for Eaf1/2 family genes from fish to mammals, which might shed some light on the molecular mechanistic basis of Eaf1 and Eaf2 in tumor suppression.
机译：EAF家族基因在多种细胞反应中起作用，例如肿瘤抑制和胚胎发育。在我们以前的工作中，发现EAF1 / 2在斑马鱼胚胎发生过程中调制收敛和延伸（C＆E）运动和模式胚胎前后轴。在这里，我们发现EAF1 / 2的损失导致斑马鱼胚胎中的扩张性Mesoderm和内胚层，并导致TGF-β因子-MZOP（TZ257）突变体中的内胚层规范的恢复，同时eAF1的发挥作用/ 2诱导细胞胚层和内胚层。 EAF缺失或过表达哺乳动物细胞中基因表达谱的分析表明EAF1和EAF2在抑制TGF-β信号中的作用被保守到哺乳动物。通过采取TGF-β报道者的优点，EAF1 / 2融合诱导蛋白和P53（M214K）突变体，我们揭示了EAF1和EAF2可以通过协同抑制无-P53和P53所需的TGF-Beta信号传导来抑制TGF-Beta转导。此外，EAF1 / 2可能与转录复合物中的TGF-β转录因子共定位和相互作用，作为靶向的阻遏物和抑制TGF-β信号传导活性。我们的研究推出了以脊椎动物中的TGF-Beta和P53的EAF1 / 2基因的先前未被识别的EAF1 / 2基因链接，并证明了从鱼到哺乳动物的EAF1 / 2家族基因的TGF-Beta抑制活性保护，这可能会在分子机制上阐明一些光线肿瘤抑制中EAF1和EAF2的基础。

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    Liu Jing-Xia; Xu Qin-Han; Li Sen; Yu XueDong; Liu Wenye; Ouyang Gang; Zhang Ting; Chen Ling-Ling;

  • 作者单位

    Huazhong Agr Univ Coll Fisheries Key Lab Freshwater Anim Breeding Minist Agr Wuhan 430070;

    Huazhong Agr Univ Coll Fisheries Key Lab Freshwater Anim Breeding Minist Agr Wuhan 430070;

    Huazhong Agr Univ Coll Informat Agr Bioinformat Key Lab Hubei Prov Wuhan 430070 Hubei Peoples;

    Huazhong Agr Univ Coll Fisheries Key Lab Freshwater Anim Breeding Minist Agr Wuhan 430070;

    Huazhong Agr Univ Coll Fisheries Key Lab Freshwater Anim Breeding Minist Agr Wuhan 430070;

    Chinese Acad Sci Inst Hydrobiol Key Lab Biodivers &

    Conservat Aquat Organisms Wuhan 430072;

    Huazhong Agr Univ Coll Fisheries Key Lab Freshwater Anim Breeding Minist Agr Wuhan 430070;

    Huazhong Agr Univ Coll Informat Agr Bioinformat Key Lab Hubei Prov Wuhan 430070 Hubei Peoples;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
  • 关键词

    Eaf1/2; TGF-beta; P53; Mesoderm; Endoderm;

    机译：EAF1 / 2;TGF-β;p53;mesoderm;endoderm;

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