Document Type
Journal ArticlePublication Date
2010-07-07Keywords
Active Transport, Cell NucleusAnimals
Animals, Genetically Modified
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Gene Expression Regulation
Insulin
Insulin-Like Growth Factor I
Longevity
Mutation
Organ Specificity
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Protein Isoforms
Proto-Oncogene Proteins c-akt
Signal Transduction
Superoxide Dismutase
Transcription Factors
Transgenes
Amino Acids, Peptides, and Proteins
Animal Experimentation and Research
Enzymes and Coenzymes
Genetic Phenomena
Genetics and Genomics
Investigative Techniques
Metadata
Show full item recordAbstract
The insulin/IGF-1 signalling (IIS) pathway has diverse roles from metabolism to longevity. In Caenorhabditis elegans, the single forkhead box O (FOXO) homologue, DAF-16, functions as the major target of the IIS pathway. One of two isoforms, DAF-16a, is known to regulate longevity, stress response and dauer diapause. 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 functions, 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.Source
Nature. 2010 Jul 22;466(7305):498-502. Epub 2010 Jul 7. Link to article on publisher's site
DOI
10.1038/nature09184Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44078PubMed ID
20613724Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/nature09184