Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego Str., 02-106 Warsaw, Poland.
Biomolecules. 2021 Jul 2;11(7):974. doi: 10.3390/biom11070974.
S100A10, a member of the S100 family of Ca-binding proteins, is a widely distributed protein involved in many cellular and extracellular processes. The best recognized role of S100A10 is the regulation, via interaction with annexin A2, of plasminogen conversion to plasmin. Plasmin, together with other proteases, induces degradation of the extracellular matrix (ECM), which is an important step in tumor progression. Additionally, S100A10 interacts with 5-hydroxytryptamine 1B (5-HT1B) receptor, which influences neurotransmitter binding and, through that, depressive symptoms. Taking this into account, it is evident that expression in the cell should be under strict control. In this work, we summarize available literature data concerning the physiological stimuli and transcription factors that influence expression. We also present our original results showing for the first time regulation of expression by grainyhead-like 2 transcription factor (GRHL2). By applying in silico analysis, we have found two highly conserved GRHL2 binding sites in the 1st intron of the gene encoding S100A10 protein. Using chromatin immunoprecipitation (ChIP) and luciferase assays, we have shown that GRHL2 directly binds to these sites and that this DNA region can affect transcription of .
S100A10 是钙结合蛋白 S100 家族的成员之一,是一种广泛分布的蛋白,参与许多细胞内和细胞外的过程。S100A10 最被人认可的作用是通过与膜联蛋白 A2 的相互作用来调节纤溶酶原向纤溶酶的转化。纤溶酶与其他蛋白酶一起诱导细胞外基质(ECM)的降解,这是肿瘤进展的重要步骤。此外,S100A10 还与 5-羟色胺 1B(5-HT1B)受体相互作用,影响神经递质的结合,并通过这种作用影响抑郁症状。考虑到这一点,很明显细胞内的 表达应该受到严格控制。在这项工作中,我们总结了有关影响 表达的生理刺激和转录因子的现有文献数据。我们还展示了我们的原始结果,首次显示颗粒头样 2 转录因子(GRHL2)调节 表达。通过计算机分析,我们在编码 S100A10 蛋白的基因的第一个内含子中发现了两个高度保守的 GRHL2 结合位点。通过染色质免疫沉淀(ChIP)和荧光素酶测定,我们已经证明 GRHL2 直接结合到这些位点,并且该 DNA 区域可以影响 的转录。