来自加拿大蒙特利尔临床研究学院(Institut de recherches cliniques de Montreal, IRCM)的研究人员最近确定出控制炎症的两个至关重要的蛋白之间的相互作用。这一重要的研究突破于近期发表在Molecular Cell期刊上。
IRCM研究人员研究了糖皮质激素(glucocorticoid)，其中糖皮质激素是一类抑制免疫系统和减少炎症的类固醇激素。它们在医学上被用来治疗过敏症、哮喘和自身免疫疾病之类的疾病。
IRCM分子遗传学研究单位主任Jacques Drouin博士解释道，“在分子生物学和遗传学上，被称作转录因子的蛋白结合到DNA上以便控制遗传信息的表达(或转录)。我们的研究定义出两种转录因子---Stat3和糖皮质激素受体(glucocorticoid receptor, GR)---在全基因组范围内的相互作用。”
尽管Stat3作用于促炎症性基因靶标(pro-inflammatory gene target)，但是糖皮质激素因它们的抗炎症性质和它们的受体GR与Stat3相互作用而被广泛地用来控制这些作用。GR能够在体内几乎每个细胞内被发现，并且能够调节控制发育、代谢、炎症反应和免疫反应的基因。
转录因子能够单独或者与其他蛋白控制信息流动：通过促进(作为激活剂)或阻断(作为抑制剂)招募特异性基因表达所需的酶。转录因子能够直接地结合到DNA上，或者将它们自己附着到另一种DNA结合蛋白上。
论文第一作者David Langlais说，“在某些情形下，根据这些蛋白如何结合到DNA序列上，它们将作出不同的表现。我们对理解为何一些转录因子能够直接结合到DNA上而作为激活剂发挥作用以及当它们被另一种蛋白招募而作为抑制剂发挥作用感到兴趣。迄今为止，这种双重作用的分子基础一直还不清楚。”(生物谷：Bioon.com)
本文编译自Controlling inflammatory and immune responses
doi:10.1016/j.molcel.2012.04.021
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The Stat3/GR Interaction Code: Predictive Value of Direct/Indirect DNA Recruitment for Transcription Outcome
David Langlais, Catherine Couture, Aurélio Balsalobre, Jacques Drouin
Transcription factor recruitment to genomic sites of action is primarily due to direct protein:DNA interactions. The subsequent recruitment of coregulatory complexes leads to either transcriptional activation or repression. In contrast to this canonical scheme, some transcription factors, such as the glucocorticoid receptor (GR), behave as transcriptional repressors when recruited to target genes through protein tethering. We have investigated the genome-wide prevalence of tethering between GR and Stat3 and found nonreciprocal interactions, namely that GR tethering to DNA-bound Stat3 results in transcriptional repression, whereas Stat3 tethering to GR results in synergism. Further, other schemes of GR and Stat3 corecruitment to regulatory modules result in transcriptional synergism, including neighboring and composite binding sites. The results indicate extensive transcriptional interactions between Stat3 and GR; further, they provide a genome-wide assessment of transcriptional regulation by tethering and a molecular basis for integration of signals mediated by GR and Stats in health and disease.
