HMG盒蛋白1抑制巨噬细胞移动抑制因子启动子的转录激活

HMG盒蛋白1（HMG box-containing protein 1, HBP1）是一种转录抑制因子. HBP1表达上调可抑制肿瘤细胞的增殖和转移,并且在肿瘤细胞中HBP1常常发生丢失或转位,这表明HBP1是一种抑癌基因. HBP1所调节的靶基因无疑将为HBP1的肿瘤抑制机制提供新的线索.本研究通过生物信息学分析发现,在促细胞增殖基因 巨噬细胞移动抑制因子（macrophage migration inhibitory factor, MIF）启动子区域-811 bp至-792 bp发现高亲和力的HBP1反应元件.缺失和突变分析表明,HBP1通过该元件抑制MIF启动子活性.此外,免疫共沉淀研究显示,HBP1在细胞内与该元件结合,并且抑制MIF的转录.功能分析进一步证实,在细胞培养液中加入重组MIF可部分消除HBP1对大肠癌细胞LOVO的抑制作用.这些结果提示,MIF是HBP1的一个靶基因.HBP1通过抑制促细胞增殖基因MIF的表达抑制肿瘤细胞生长.     

The embryonic expression patterns of zfh-1 and zfh-2, two Drosophila genes encoding novel zinc-finger homeodomain proteins.

The zfh-1 and zfh-2 genes of D. melanogaster encode novel proteins containing both homeodomain and C2-H2 zinc-finger DNA-binding motifs. Antisera against these proteins were used to investigate their expression patterns during embryonic development. The zfh-1 gene is expressed in the mesoderm of early embryos and in a number of mesodermally-derived structures of late embryos, including the dorsal vessel, support cells of the gonads, and segment-specific arrays of adult muscle precursors. In addition, zfh-1 is expressed in the majority of identified motor neurons of the developing CNS. The mesodermal zfh-1 expression requires the products of the twist and snail genes. The zfh-2 gene displays a more limited expression pattern, largely restricted to the CNS of late embryos. Ubiquitous zfh-1 expression in transgenic flies bearing an hsp70-zfh-1 construct has specific developmental consequences, including embryonic CNS defects as well as adult eye and bristle abnormalities. The expression patterns of zfh-1 and zfh-2 suggest that both genes may be involved in Drosophila neurogenesis and that zfh-1 may have additional functions in mesoderm development.