Picozzi Paola, Wang Fengxiang, Cronk Kevin, Ryan Kenneth
Department of Pediatrics, Division of Cardiology, Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA.
J Biol Chem. 2009 Jan 23;284(4):2397-408. doi: 10.1074/jbc.M808704200. Epub 2008 Nov 26.
The T-box gene Eomesodermin (Eomes) is required for early embryonic mesoderm differentiation in mouse, frog (Xenopus laevis), and zebrafish, is important in late cardiac development in Xenopus, and for CD8+ T effector cell function in mouse. Eomes can ectopically activate many mesodermal genes. However, the mechanism by which Eomes activates transcription of these genes is poorly understood. We report that Eomes protein interacts with Smad2 and is capable of working in a non-cell autonomous manner via transfer of Eomes protein between adjacent embryonic cells. Blocking of Eomes protein transfer using a farnesylated red fluorescent protein (CherryF) also prevents Eomes nuclear accumulation. Transfer of Eomes protein between cells is mediated by the Eomes carboxyl terminus (456-692). A carbohydrate binding domain within the Eomes carboxyl-terminal region is sufficient for transfer and important for gene activation. We propose a novel mechanism by which Eomes helps effect a cellular response to a morphogen gradient.
T-box基因Eomesodermin（Eomes）在小鼠、青蛙（非洲爪蟾）和斑马鱼的早期胚胎中胚层分化过程中是必需的，在非洲爪蟾的晚期心脏发育中起重要作用，并且对小鼠的CD8 + T效应细胞功能也很重要。Eomes可以异位激活许多中胚层基因。然而，Eomes激活这些基因转录的机制仍知之甚少。我们报告称，Eomes蛋白与Smad2相互作用，并且能够通过相邻胚胎细胞之间Eomes蛋白的转移以非细胞自主方式发挥作用。使用法尼基化红色荧光蛋白（CherryF）阻断Eomes蛋白转移也会阻止Eomes的核积累。细胞间Eomes蛋白的转移由Eomes羧基末端（456 - 692）介导。Eomes羧基末端区域内的碳水化合物结合结构域足以实现转移，并且对基因激活很重要。我们提出了一种新机制，通过该机制Eomes有助于实现细胞对形态发生素梯度的反应。
