Mukhopadhyay Arnab, Oh Seung Wook, Tissenbaum Heidi A
Program in Gene Function and Expression, Program in Molecular Medicine, Aaron Lazare Research Building, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Exp Gerontol. 2006 Oct;41(10):928-34. doi: 10.1016/j.exger.2006.05.020. Epub 2006 Jul 12.
In Caenorhabditis elegans, the insulin/IGF-1 signaling pathway controls many biological processes such as life span, fat storage, dauer diapause, reproduction and stress response . This pathway is comprised of many genes including the insulin/IGF-1 receptor (DAF-2) that signals through a conserved PI 3-kinase/AKT pathway and ultimately down-regulates DAF-16, a forkhead transcription factor (FOXO). DAF-16 also receives input from several other pathways that regulate life span such as the germline and the JNK pathway [Hsin, H., Kenyon, C., 1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366; Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494-4499]. Therefore, DAF-16 integrates signals from multiple pathways and regulates its downstream target genes to control diverse processes. Here, we discuss the signals to and from DAF-16, with a focus on life span regulation.
在秀丽隐杆线虫中，胰岛素/胰岛素样生长因子-1（IGF-1）信号通路控制着许多生物学过程，如寿命、脂肪储存、 dauer 滞育、繁殖和应激反应。该通路由许多基因组成，包括通过保守的磷脂酰肌醇3-激酶/蛋白激酶B（PI 3-激酶/AKT）信号通路发挥作用并最终下调叉头转录因子DAF-16的胰岛素/IGF-1受体（DAF-2）。DAF-16还接收来自其他几个调节寿命的信号通路的输入，如生殖系和JNK信号通路[Hsin, H., Kenyon, C., 1999. 来自生殖系统的信号调节秀丽隐杆线虫的寿命。《自然》399, 362 - 366；Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK通过调节叉头转录因子/DAF-16的核转位来调节秀丽隐杆线虫的寿命。《美国国家科学院院刊》102, 4494 - 4499]。因此，DAF-16整合来自多个信号通路的信号并调节其下游靶基因，以控制多种生物学过程。在这里，我们讨论与DAF-16相关的信号，重点是寿命调节。
