Department Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Chemistry. 2022 Jan 3;28(1):e202103030. doi: 10.1002/chem.202103030. Epub 2021 Nov 22.
Macrophage migration inhibitory factor (MIF) and its homolog MIF2 (also known as D-dopachrome tautomerase or DDT) play key roles in cell growth and immune responses. MIF and MIF2 expression is dysregulated in cancers and neurodegenerative diseases. Accurate and convenient detection of MIF and MIF2 will facilitate research on their roles in cancer and other diseases. Herein, we report the development and application of a 4-iodopyrimidine based probe 8 for the selective labeling of MIF and MIF2. Probe 8 incorporates a fluorophore that allows in situ imaging of these two proteins. This enabled visualization of the translocation of MIF2 from the cytoplasm to the nucleus upon methylnitronitrosoguanidine stimulation of HeLa cells. This observation, combined with literature on nuclease activity for MIF, enabled the identification of nuclease activity for MIF2 on human genomic DNA.
巨噬细胞移动抑制因子(MIF)及其同系物 MIF2(也称为 D-多巴色素互变异构酶或 DDT)在细胞生长和免疫反应中发挥关键作用。MIF 和 MIF2 的表达在癌症和神经退行性疾病中失调。MIF 和 MIF2 的准确便捷检测将有助于研究它们在癌症和其他疾病中的作用。本文报道了一种基于 4-碘嘧啶的探针 8 的开发和应用,用于选择性标记 MIF 和 MIF2。探针 8 包含一个荧光团,允许原位成像这两种蛋白质。这使得能够观察到甲基亚硝脲刺激 HeLa 细胞时 MIF2 从细胞质向核内的易位。这一观察结果,结合关于 MIF 的核酸酶活性的文献,使人们能够识别人基因组 DNA 上 MIF2 的核酸酶活性。