Sgarra Riccardo, Zammitti Salvina, Lo Sardo Alessandra, Maurizio Elisa, Arnoldo Laura, Pegoraro Silvia, Giancotti Vincenzo, Manfioletti Guidalberto
Department of Life Sciences, University of Trieste, via L. Giorgieri, 1-34127 Trieste, Italy.
Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):37-47. doi: 10.1016/j.bbagrm.2009.08.009. Epub 2009 Sep 2.
Nuclear functions rely on the activity of a plethora of factors which mostly work in highly coordinated molecular networks. The HMGA proteins are chromatin architectural factors which constitute critical hubs in these networks. HMGA are referred to as oncofetal proteins since they are highly expressed and play essential functions both during embryonic development and neoplastic transformation. A particular feature of HMGA is their intrinsically disordered status, which confers on them an unusual plasticity in contacting molecular partners. Indeed these proteins are able to bind to DNA at the level of AT-rich DNA stretches and to interact with several nuclear factors. In the post-genomic era, and with the advent of proteomic tools for the identification of protein-protein interactions, the number of HMGA molecular partners has increased rapidly. This has led to the extension of our knowledge of the functional involvement of HMGA from the transcriptional regulation field to RNA processing, DNA repair, and chromatin remodeling and dynamics. This review focuses mainly on the protein-protein interaction network of HMGA and its functional outcome. HMGA molecular partners have been functionally classified and all the information collected in a freely available database (http://www.bbcm.units.it/ approximately manfiol/INDEX.HTM).
核功能依赖于大量因子的活性，这些因子大多在高度协调的分子网络中发挥作用。HMGA蛋白是染色质结构因子，构成了这些网络中的关键枢纽。HMGA被称为癌胚蛋白，因为它们在胚胎发育和肿瘤转化过程中均高度表达并发挥重要功能。HMGA的一个特殊特征是其内在无序状态，这赋予它们在与分子伴侣接触时具有不同寻常的可塑性。实际上，这些蛋白能够在富含AT的DNA片段水平上与DNA结合，并与多种核因子相互作用。在后基因组时代，随着用于鉴定蛋白质-蛋白质相互作用的蛋白质组学工具的出现，HMGA分子伴侣的数量迅速增加。这使得我们对HMGA功能参与的认识从转录调控领域扩展到RNA加工、DNA修复以及染色质重塑和动力学。本综述主要关注HMGA的蛋白质-蛋白质相互作用网络及其功能结果。HMGA分子伴侣已进行功能分类，所有收集到的信息都存于一个免费数据库中（http://www.bbcm.units.it/ approximately manfiol/INDEX.HTM）。
