School of Molecular Bioscience, The University of Sydney, Sydney, New South Wales, Australia.
PLoS One. 2012;7(6):e39218. doi: 10.1371/journal.pone.0039218. Epub 2012 Jun 19.
The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1.
LMO4 和 DEAF1 蛋白有助于乳腺上皮细胞的增殖。在乳腺癌中,LMO4 上调,影响其与其他蛋白伴侣的相互作用。这可能使细胞走上肿瘤形成的道路。LMO4 和 DEAF1 相互作用,但尚不清楚它们如何合作来调节细胞增殖。在这项研究中,我们确定了 DEAF1 中 LMO4 的一个特定结合域。该结构域包含一个无结构区域,该区域可直接与 LMO4 接触,以及一个卷曲螺旋,其中包含 DEAF1 的核输出信号(NES)。卷曲螺旋区可以形成四聚体,并具有卷曲螺旋结构域的典型特性。使用简单的基于细胞的测定法,我们表明 LMO4 调节 DEAF NES 的活性,导致包含 DEAF1 的 LMO4 相互作用区域的构建体在核内积累。