Institute for Biochemistry, Westfälische-Wilhelms-Universität, Münster, Germany.
Leukemia. 2012 Apr;26(4):615-22. doi: 10.1038/leu.2011.275. Epub 2011 Oct 11.
The c-myb proto-oncogene encodes a transcription factor that is highly expressed in the progenitor cells of the hematopoietic system, where it regulates the expression of genes important for lineage determination, cell proliferation and differentiation. There is strong evidence that deregulation of c-myb expression is involved in the development of human tumors, particularly of certain types of leukemia, and breast and colon cancer. The c-Myb protein is therefore an interesting therapeutic target. Here, we have investigated the potential of natural sesquiterpene lactones (STLs), a class of compounds that are active constituents of a variety of medicinal plants, to suppress Myb-dependent gene expression. We have developed a test system that allows screening of compounds for their ability to interfere with the activation of Myb target genes. Using this assay system, we have identified the STL mexicanin-I as the first cell-permeable, low-molecular-weight inhibitor of Myb-induced gene expression.
c-myb 原癌基因编码一种转录因子，在造血系统的祖细胞中高度表达，在那里它调节对谱系决定、细胞增殖和分化重要的基因的表达。有强有力的证据表明，c-myb 表达的失调参与了人类肿瘤的发展，特别是某些类型的白血病、乳腺癌和结肠癌。因此，c-Myb 蛋白是一个有趣的治疗靶点。在这里，我们研究了天然倍半萜内酯（STLs）的潜力，STLs 是多种药用植物的活性成分，能够抑制 Myb 依赖性基因表达。我们开发了一种测试系统，允许筛选化合物干扰 Myb 靶基因激活的能力。使用该测定系统，我们已经确定 STL 墨西哥麻素-I 是第一个细胞通透性、低分子量的 Myb 诱导基因表达抑制剂。
