The Snail-like CES-1 protein of C-elegans can block the expression of the BH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH proteins
The Snail-like CES-1 protein of C-elegans can block the expression of the BH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH proteins
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DOI：
10.1242/dev.00597
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发表时间：
2003-09-01
期刊：
影响因子：
4.6
通讯作者：
Conradt, B
中科院分区：
文献类型：
--
作者：
Thellmann, M;Hatzold, J;Conradt, B
秀丽隐杆线虫的NSM细胞分化成神经元，而它们的姐妹篇，NSM姐妹细胞，在胚胎发生期间经历程序性细胞死亡。NSM姐妹细胞的程序性死亡依赖于细胞死亡激活剂EGL-1，这是一种在线虫中程序性细胞死亡所需的仅含BH 3的蛋白质，并且可以通过细胞死亡特异性基因ces-1中的功能获得（gf）突变来防止，ces-1编码蜗牛样DNA结合蛋白。在这里，我们表明，基因hlh-2和hlh-3，分别编码一个Daughterless样和Achaete-盾甲藻样bHLH蛋白，需要杀死NSM姐妹细胞。由HLH-2和HLH-3组成的异源二聚体HLH-2/HLH-3在体外与egl-1基因座的顺式调节区中的Snail结合位点/E-box结合，这是体内NSM姐妹细胞死亡所必需的。因此，我们认为HLH-2/HLH-3是egl-1转录的直接的、细胞类型特异性激活剂。此外，Snail样CES-1蛋白可以通过egl-1基因座中相同的Snail结合位点/E盒起作用来阻断NSM姐妹细胞的死亡。因此，在ces-1（gf）动物中，CES-1可能通过成功地与HLH-2/HLH-3竞争结合egl-1基因座来防止NSM姐妹细胞的死亡。
The NSM cells of the nematode Caenorhabditis elegans differentiate into serotonergic neurons, while their sisters, the NSM sister cells, undergo programmed cell death during embryogenesis. The programmed death of the NSM sister cells is dependent on the cell-death activator EGL-1, a BH3-only protein required for programmed cell death in C elegans, and can be prevented by a gain-of-function (gf) mutation in the cell-death specification gene ces-1, which encodes a Snail-like DNA-binding protein. Here, we show that the genes hlh-2 and hlh-3, which encode a Daughterless-like and an Achaete-scute-like bHLH protein, respectively, are required to kill the NSM sister cells. A heterodimer composed of HLH-2 and HLH-3, HLH-2/HLH-3, binds to Snail-binding sites/E-boxes in a cis-regulatory region of the egl-1 locus in vitro that is required for the death of the NSM sister cells in vivo. Hence, we propose that HLH-2/HLH-3 is a direct, cell-type specific activator of egl-1 transcription. Furthermore, the Snail-like CES-1 protein can block the death of the NSM sister cells by acting through the same Snail-binding sites/E-boxes in the egl-1 locus. In ces-1(gf) animals, CES-1 might therefore prevent the death of the NSM sister cells by successfully competing with HLH-2/HLH-3 for binding to the egl-1 locus.