C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO.
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.
Wang
Yamei
Y
Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01605, USA.
Oh
Seung Wook
SW
Deplancke
Bart
B
Luo
Jianyuan
J
Walhout
Albertha J M
AJ
Tissenbaum
Heidi A
HA
D048948:14-3-3 Proteins / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism* / Q000502:physiology*; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015151:Immunoblotting; D008136:Longevity; D023421:Models, Animal; D030781:Organisms, Genetically Modified; D034622:RNA Interference; 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; C106207:par-5 protein, C elegans; D049452:Green Fluorescent Proteins; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins