A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins.
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.
Berdichevsky
Ala
A
Department of Biology, Massachusetts Insitute of Technology, Cambridge, Massachusetts 02139, USA.
Guarente
Leonard
L
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018384:Oxidative Stress; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins