Analysis of the structure and interaction of apoptotic signaling molecules via Fas

死亡效应域（death effector domain， DED）参与细胞凋亡信号转导，是蛋白质相互作用的重要组成部分。半胱氨酸蛋白酶caspase-8和病毒蛋白MC159分别有两个串联重复的DEDs。caspase-8的DEDs可诱导细胞凋亡，而MC159的DEDs可抑制细胞凋亡。为了检测DED结构域的结合和生物活性，我们产生了caspase-8和MC159衍生的DED缺失和嵌合体突变体。与野生型caspase-8和MC159相比，这些突变体不起作用。因此，我们得出结论，两个重复的DEDs的结合对于含有ed的蛋白刺激或抑制细胞凋亡是必要的。通过在Genbank数据库中搜索含有ded的蛋白，我们发现了一个在氨基末端含有两个串联重复ded的新分子。我们通过northern blot分析在小鼠睾丸中检测到这些分子的高表达。我们推测该分子可能具有信号转导的新功能。

The death effector domain(DED), which is essential for protein interaction, is involved in apoptotic signal transudation. Cysteine protease caspase-8 and viral protein MC159 have two tandemly repeated DEDs, respectively. The DEDs of caspase-8 could induce apoptosis whereas that of MC159 inhibits apoptosis. To examine binding and biological activities of the DED domains, we generated deletion and chimera mutants of DEDs derived from caspase-8 and MC159. These mutants did not work compare to wild type of caspase-8 and MC159. Therefore, we concluded that the combination of the two-repeated DEDs is necessary for the DED-containing proteins to stimulate or inhibit apoptosis.By searching DED-containing proteins on Genbank database, we found a new molecule which contains two tandemly repeated DEDs at the amino-terminal portion. We detected high expression of this molecules in the mouse testis by northern blot analysis. We suppose that this molecule may have a new function for signal transduction.