A Stress Response Pathway Involving Sirtuins, Forkhead and 14-3-3 Proteins

Ala Berdichevsky and Leondard Guarente

volume 5 | issue 22

15 november 2006
Pages: 2588 - 2591

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A conserved sir2 deacetylase gene can determine longevity of yeast, flies, and worms. Recently we have reported a molecular mechanism of action of the C. elegans homologue sir-2.1. Our study revealed a novel stress-dependent pathway for lifespan determination in which SIR-2.1 binds to 14-3-3 proteins and a forkhead transcription factor DAF-16 to activate transcription of DAF-16 target genes. DAF-16 has long been known as a central protein in the regulation of lifespan that interfaces with multiple pathways. Recent studies by us and other laboratories suggest that DAF-16 requires co-factors for full activity. In this prospective we review recent literature highlighting the role of SIR-2.1, 14-3-3, and other DAF-16 co-factors in DAF-16 activation.

Authors

Ala Berdichevsky

MIT; Cambridge, MA USA

Leondard Guarente

MIT; Cambridge, MA USA

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: