Nutrient isothiocyanates covalently modify and inhibit the inflammatory cytokine macrophage migration inhibitory factor (MIF).
Nutrient isothiocyanates covalently modify and inhibit the inflammatory cytokine macrophage migration inhibitory factor (MIF).
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DOI：
10.1042/bj20091170
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发表时间：
2009-10-12
期刊：
影响因子：
--
通讯作者：
Templeton DJ
中科院分区：
文献类型：
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作者：
Cross JV;Rady JM;Foss FW;Lyons CE;Macdonald TL;Templeton DJ
膳食异硫氰酸酯（ITC）预防癌症并在体内显示其他生物活性。作为亲电体，ITC可以共价修饰细胞蛋白质。使用一种新的蛋白质组学筛选，我们确定了巨噬细胞迁移抑制因子（MIF）作为完整细胞中营养ITCs的主要靶标。ITCs共价修饰MIF的氨基末端脯氨酸残基并消除其催化互变异构酶活性。MIF缺陷不能阻止诱导2期基因表达，这是许多癌症化学预防剂（包括ITC）的标志。由于MIF在控制恶性细胞生长中的新兴作用及其明显参与炎症，营养ITCs对MIF的抑制提示了炎性疾病和癌症的治疗策略。
Dietary isothiocyanates (ITCs) prevent cancer and show other bioactivities in vivo. As electrophiles, ITCs may covalently modify cellular proteins. Using a novel proteomics screen, we identified the Macrophage Migration Inhibitory Factor (MIF) as the principal target of nutrient ITCs in intact cells. ITCs covalently modify the amino-terminal proline residue of MIF and extinguish its catalytic tautomerase activity. MIF deficiency does not prevent induction of Phase 2 gene expression, a hallmark of many cancer chemopreventives including ITCs. Due to the emerging role of MIF in control of malignant cell growth and its clear involvement in inflammation, inhibition of MIF by nutrient ITCs suggests therapeutic strategies for inflammatory diseases and cancer.