Ookuma Sadatsugu, Fukuda Makoto, Nishida Eisuke
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Curr Biol. 2003 Mar 4;13(5):427-31. doi: 10.1016/s0960-9822(03)00108-8.
In Caenorhabditis elegans, an insulin-like signaling pathway, which includes the daf-2 and age-1 genes, controls longevity and stress resistance. Downregulation of this pathway activates the forkhead transcription factor DAF-16, whose transcriptional targets are suggested to play an essential role in controlling the phenotypes governed by this pathway. We have surveyed the genes that have the DAF-16 consensus binding element (DBE) within putative regulatory regions. Here, we show that one such gene, termed scl-1, is a positive regulator of longevity and stress resistance. Expression of scl-1 is upregulated in long-lived daf-2 and age-1 mutants and is undetectable in a short-lived daf-16 mutant. SCL-1 is a putative secretory protein with an SCP domain and is homologous to the mammalian cysteine-rich secretory protein (CRISP) family. scl-1 is required for the extension of the life span of daf-2 and age-1 mutants, and downregulation of scl-1 reduces both life span and stress resistance of this animal. SCL-1, whose expression is dependent on DAF-16, is the first example of a putative secretory protein that positively regulates longevity and stress resistance.
在秀丽隐杆线虫中，一条包括daf-2和age-1基因的胰岛素样信号通路控制着寿命和抗逆性。该通路的下调会激活叉头转录因子DAF-16，其转录靶点被认为在控制该通路所决定的表型中起关键作用。我们已经对在假定调控区域内具有DAF-16共有结合元件（DBE）的基因进行了调查。在此，我们表明，一个名为scl-1的此类基因是寿命和抗逆性的正向调节因子。scl-1的表达在长寿的daf-2和age-1突变体中上调，而在短命的daf-16突变体中无法检测到。SCL-1是一种具有SCP结构域的假定分泌蛋白，与哺乳动物富含半胱氨酸的分泌蛋白（CRISP）家族同源。scl-1是daf-2和age-1突变体延长寿命所必需的，而scl-1的下调会降低这种动物的寿命和抗逆性。SCL-1的表达依赖于DAF-16，它是第一个正向调节寿命和抗逆性的假定分泌蛋白的例子。
