Worming pathways to and from DAF-16/FOXO
Program in Gene Function and Expression
Medical Subject Headings
Aging; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Caloric Restriction; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Germ Cells; Insulin; Longevity; Models, Genetic; Receptor, IGF Type 2; Receptor, Insulin; Signal Transduction; Sirtuins; Transcription Factors
Genetics and Genomics
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.
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Citation: Exp Gerontol. 2006 Oct;41(10):928-34. Epub 2006 Jul 12. Link to article on publisher's site