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往返DAF-16/FOXO的信号通路

Worming pathways to and from DAF-16/FOXO.

作者信息

Mukhopadhyay Arnab, Oh Seung Wook, Tissenbaum Heidi A

机构信息

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.

出版信息

Exp Gerontol. 2006 Oct;41(10):928-34. doi: 10.1016/j.exger.2006.05.020. Epub 2006 Jul 12.

Abstract

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.

摘要

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。

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