C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO
Program in Gene Function and Expression; Program in Molecular Medicine; Department of Cancer Biology
Medical Subject Headings
14-3-3 Proteins; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Green Fluorescent Proteins; Immunoblotting; Longevity; Models, Animal; Organisms, Genetically Modified; RNA Interference; Sirtuins; Transcription Factors
Genetics and Genomics
14-3-3 proteins are evolutionarily conserved and ubiquitous proteins that function in a wide variety of biological processes. Here we define a new role for C. elegans 14-3-3 proteins in life span regulation. We identify two C. elegans 14-3-3 proteins as interacting proteins of a major life span regulator, the C. elegans SIR2 ortholog, SIR-2.1. Similar to sir-2.1, we find that overexpression of either 14-3-3 protein (PAR-5 or FTT-2) extends life span and that this is dependent on DAF-16, a forkhead transcription factor (FOXO), another important life span regulator in the insulin/IGF-1 signaling pathway. Furthermore, we show that both 14-3-3 proteins are co-expressed with DAF-16 and SIR-2.1 in the tissues critical for life span regulation. Finally, we show that DAF-16/FOXO also physically interacts with the 14-3-3 proteins. These results suggest that C. elegans 14-3-3 proteins can regulate longevity by cooperating with both SIR-2.1 and DAF-16/FOXO.
Rights and Permissions
Citation: Mech Ageing Dev. 2006 Sep;127(9):741-7. Epub 2006 Jul 24. Link to article on publisher's site