Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
Nucleic Acids Res. 2010 May;38(9):2799-812. doi: 10.1093/nar/gkq013. Epub 2010 Jan 25.
Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolin-bound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase C, which is accompanied with alterations in cell proliferation and apoptosis. We propose a model for the regulation of these genes, which brings a new insight into the molecular mechanisms that control cellular transformation driven by activation of protein kinases.
非恶性细胞可以通过激活控制神经抑制因子（REST）降解的激酶来转化。在这里，我们确定了一种有助于基因激活的机制，其表达受含有 REST 和核仁素重叠结合位点的反应元件控制。我们证明，磷酸化和非磷酸化的核仁素结合 DNA；然而，只有磷酸化核仁素才能成功地与全长 REST 或源自 REST 的 DNA 结合肽 REST68 竞争，以与重叠结合位点结合。我们表明，这两种转录因子之间的相互作用调节了蛋白激酶激活的肿瘤和非恶性细胞中细胞存活和免疫调节基因的激活，伴随着细胞增殖和凋亡的改变。我们提出了一个调节这些基因的模型，为控制由蛋白激酶激活驱动的细胞转化的分子机制提供了新的见解。
