西亚试剂：A new DAF-16 isoform regulates longevity

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.

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