FOXO (single Forkhead Box O) 转录因子已成为细胞功能调控因子的一个主要汇聚点，包括“胰岛素/IGF1信号作用(IIS)通道”。IIS参与各种不同的生物过程，包括寿命的调控。在线虫中，FOXO转录因子DAF-16a在IIS通道中扮演一个主要角色。DAF-16a是两个同形物中的一个，调控线虫的寿命、应激反应和“多尔滞育”(dauer diapause)，但尚不清楚DAF-16在调控这些不同生物过程中是怎样实现其特异性的。
现在，一个新的DAF-16同形物，即DAF-16d/f，已被识别出来，它在寿命调控中也很重要。一系列涉及基因表达操纵的实验表明，各种不同DAF-16同形物之间的组合互动的作用是，在整个生物的背景下微调由IIS调控的过程。线虫似乎是利用来自一个基因的多种同形物来微调由IIS调控的过程的，这与哺乳动物中的情况形成对比――在哺乳动物中，四个不同的FOXO基因执行重叠的和截然不同的功能。(生物谷Bioon.com)
生物谷推荐原文出处：
Nature doi:10.1038/nature09184
A new DAF-16 isoform regulates longevity
Eun-Soo Kwon,Sri Devi Narasimhan,Kelvin Yen" Heidi A. Tissenbaum
The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity1, 2, 3, 4, 5. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway2, 3, 6, 7. One of two isoforms4, 5, 8, DAF-16a, is known to regulate longevity, stress response and dauer diapause8, 9, 10, 11. However, it remains unclear how DAF-16 achieves its specificity in regulating these various biological processes. Here we identify a new isoform, DAF-16d/f, as an important isoform regulating longevity. We show that DAF-16 isoforms functionally cooperate to modulate IIS-mediated processes through differential tissue enrichment, preferential modulation by upstream kinases, and regulating distinct and overlapping target genes. Promoter-swapping experiments show both the promoter and the coding region of DAF-16 are important for its function. Importantly, in mammals, four FOXO genes have overlapping and different functions6, 12, and in C. elegans, a single FOXO/DAF-16 uses distinct isoforms to fine-tune the IIS-mediated processes in the context of a whole organism.
