Department of Molecular Microbiology, Technion-Israel Institute of Technology, 31096 Haifa, Israel.
Cell Microbiol. 2012 Jan;14(1):58-70. doi: 10.1111/j.1462-5822.2011.01697.x. Epub 2011 Sep 30.
Adaptation to environmental stress is a key process that allows the unicellular parasite Entamoeba histolytica to survive in its human host. We previously characterized EhMLBP as an essential protein for the growth and the virulence of the parasite. EhMLBP binds to methylated repetitive DNA, and is one of the core proteins of the parasite's epigenetic machinery. Here, we show that EhMLBP and heat shock proteins have common properties. EhMLBP is induced by heat shock and its expression is regulated by a heat shock element binding site that is located in its 5' non-coding region. Following heat shock, the perinuclear localization of EhMLBP in control trophozoites is replaced by an even distribution within the nucleus alongside with an enhanced recruitment of EhMLBP to the reverse transcriptase of a long interspersed nucleotide element (LINE) DNA. Constitutive overexpression of EhMLBP protects trophozoites against heat shock and reduces protein aggregation. This protective function is lost in trophozoites that overexpress a mutated form of EhMLBP which is devoid of its heat shock domain. To the best of our knowledge, this is the first report of a methyl DNA-binding protein that plays a protective role against heat shock.
适应环境压力是单细胞寄生虫溶组织内阿米巴生存于其人类宿主的关键过程。我们之前的研究表明 EhMLBP 是寄生虫生长和毒力所必需的蛋白。EhMLBP 与甲基化重复 DNA 结合，是寄生虫表观遗传机制的核心蛋白之一。在这里，我们发现 EhMLBP 和热休克蛋白具有共同的特性。EhMLBP 可被热激诱导，其表达受位于其 5'非编码区的热休克元件结合位点调控。热激后，EhMLBP 在对照滋养体中的核周定位被取代，均匀分布于核内，同时 EhMLBP 与长散在核元件（LINE）DNA 的逆转录酶的募集增强。EhMLBP 的组成性过表达可保护滋养体免受热激，并减少蛋白聚集。在过度表达缺乏热激结构域的 EhMLBP 突变形式的滋养体中，这种保护功能丧失。据我们所知，这是第一个报道甲基化 DNA 结合蛋白在热激中发挥保护作用的报告。
