Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain
Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain
复制标题
DOI：
10.1016/j.jmb.2006.02.020
复制
发表时间：
2006-05-12
影响因子：
5.6
通讯作者：
Jayaraman, Padma-Sheela
中科院分区：
文献类型：
--
作者：
Soufi, Abdenour;Smith, Corinne;Jayaraman, Padma-Sheela
同源结构域蛋白通过改变基因表达时间和组织特异性方式调节多种发育途径。富含脯氨酸的同源结构域蛋白（PRH/Hex）是一种转录因子，是胚胎发育和造血的重要调节因子。最近的发现表明自缔合是转录因子功能的一个重要特征。在这里，我们显示使用各种技术，包括凝胶过滤，分析ultracenthagation，电子显微镜和体外交联，纯化的重组PRH是低聚的，我们使用体内交联，以确认这种蛋白质存在的低聚物在细胞中。这是首次证明同源结构域蛋白可以在体内寡聚化。与这些研究结果相一致，我们发现，一小部分内源性和外源性PRH出现在细胞核内和核周围的离散病灶。PRH的N端结构域参与细胞增殖和转录抑制的调控，并能进行多种蛋白质-蛋白质相互作用。我们发现，该地区的PRH包含一个新的脯氨酸丰富的二聚化结构域，介导的寡聚化。我们提出了一个模型，解释PRH如何形成寡聚体，我们讨论这些寡聚体可能会控制转录。(c)2006爱思唯尔有限公司保留所有权利。
Homeodomain proteins regulate multiple developmental pathways by altering gene expression temporally and in a tissue-specific fashion. The Proline Rich Homeodomain protein (PRH/Hex) is a transcription factor and an essential regulator of embryonic development and haematopoiesis. Recent discoveries have implicated self-association as an important feature of transcription factor function. Here, we show using a variety of techniques including gel-filtration, analytical ultracentrifugation, electron microscopy and in vitro cross-linking, that purified recombinant PRH is oligomeric and we use in vivo cross-linking to confirm that this protein exists as oligomers in cells. This is the first demonstration that a homeodomain protein can oligomerise in vivo. Consistent with these findings we show that a fraction of endogenous and exogenous PRH appears as discrete foci within the nucleus and at the nuclear periphery. The N-terminal domain of PRH is involved in the regulation of cell proliferation and transcriptional repression and can make multiple protein-protein interactions. We show that this region of PRH contains a novel proline-rich dimerisation domain that mediates oligomerisation. We propose a model that explains how PRH forms oligomers and we discuss how these oligomers might control transcription. (c) 2006 Elsevier Ltd. All rights reserved.