Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila.
Increased expression of the histone deacetylase sir2 has been reported to extend the life span of diverse organisms including yeast, Caenorhabditis elegans, and Drosophila melanogaster. A small molecule activator of Sir2, resveratrol, has also been suggested to extend the fitness and survival of these simple model organisms as well as mice fed high calorie diets. However, other studies in yeast have shown that Sir2 itself may prevent life extension, and high expression levels of Sir2 can be toxic to yeast and mouse cells. This conflicting evidence highlights the importance of understanding the mechanisms by which Sir2 expression or activation affects survival of organisms. To investigate the downstream signaling pathways affected by Sir2 in Drosophila, we generated transgenic flies expressing sir2. Here, we show that overexpression of sir2 in Drosophila promotes caspase-dependent but p53-independent apoptosis that is mediated by the JNK and FOXO signaling pathways. Furthermore, we find that a loss-of-function sir2 mutant partially prevents apoptosis induced by UV irradiation in the eye. Together, these results suggest that Sir2 normally participates in the regulation of cell survival and death in Drosophila.
Griswold
Anthony J
AJ
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Chang
Karen T
KT
Runko
Alexander P
AP
Knight
Melanie A
MA
Min
Kyung-Tai
KT
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002470:Cell Survival; D004330:Drosophila / Q000196:embryology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D010641:Phenotype; D037761:Sirtuins / Q000378:metabolism*; D014466:Ultraviolet Rays
D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; C447899:Sirt2 protein, Drosophila; D037761:Sirtuins; D006655:Histone Deacetylases