Kuzuhara T, Suganuma M, Oka K, Fujiki H
Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Biochem Biophys Res Commun. 2007 Nov 3;362(4):805-10. doi: 10.1016/j.bbrc.2007.08.058. Epub 2007 Aug 22.
Tumor necrosis factor-alpha (TNF-alpha) inducing protein (Tipalpha) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-alpha and chemokine genes and activation of nuclear factor-kappaB. Since Tipalpha enters gastric cancer cells, the Tipalpha binding molecules in the cells should be investigated. The direct DNA-binding activity of Tipalpha was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tipalpha and DNA, revealed that the affinity of Tipalpha for (dGdC)10 is 2400 times stronger than that of del-Tipalpha, an inactive Tipalpha. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tipalpha. And the DNA-binding activity of Tipalpha was first demonstrated with a molecule secreted from H. pylori.
肿瘤坏死因子-α(TNF-α)诱导蛋白(Tipα)是幽门螺杆菌(H. pylori)分泌的一种致癌因子,通过增强TNF-α和趋化因子基因的表达以及激活核因子-κB来介导。由于Tipα进入胃癌细胞,因此应研究细胞中的Tipα结合分子。使用单链和双链基因组DNA纤维素通过下拉试验观察到Tipα的直接DNA结合活性。表面等离子体共振分析表明Tipα与DNA之间存在关联,结果显示Tipα对(dGdC)10的亲和力比无活性的Tipα(del-Tipα)强2400倍。这表明Tipα的DNA结合活性与致癌活性之间存在很强的相关性。并且Tipα的DNA结合活性首次在幽门螺杆菌分泌的一种分子中得到证实。