Cross Janet V, Rady Joshua M, Foss Frank W, Lyons Charles E, Macdonald Timothy L, Templeton Dennis J
Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Biochem J. 2009 Oct 12;423(3):315-21. doi: 10.1042/BJ20091170.
Dietary ITCs (isothiocyanates) prevent cancer and show other bioactivities in vivo. As electrophiles, ITCs may covalently modify cellular proteins. Using a novel proteomics screen, we identified MIF (macrophage migration inhibitory factor) as the principal target of nutrient ITCs in intact cells. ITCs covalently modify the N-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 the 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.
膳食异硫氰酸酯（ITCs）可预防癌症，并在体内表现出其他生物活性。作为亲电试剂，ITCs可能会与细胞蛋白发生共价修饰。通过一项新型蛋白质组学筛选，我们确定巨噬细胞迁移抑制因子（MIF）是完整细胞中营养性ITCs的主要靶点。ITCs与MIF的N端脯氨酸残基发生共价修饰，并消除其催化互变异构酶活性。MIF缺乏并不妨碍II相基因表达的诱导，II相基因表达是包括ITCs在内的许多癌症化学预防剂的一个标志。由于MIF在控制恶性细胞生长中的新作用及其在炎症中的明确参与，营养性ITCs对MIF的抑制提示了针对炎症性疾病和癌症的治疗策略。
