Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling.
In Drosophila melanogaster, p53 (Dmp53) is an important mediator of longevity. Expression of dominant-negative (DN) forms of Dmp53 in adult neurons, but not in muscle or fat body cells, extends lifespan. The lifespan of calorie-restricted flies is not further extended by simultaneously expressing DN-Dmp53 in the nervous system, indicating that a decrease in Dmp53 activity may be a part of the CR lifespan-extending pathway in flies. In this report, we show that selective expression of DN-Dmp53 in only the 14 insulin-producing cells (IPCs) in the brain extends lifespan to the same extent as expression in all neurons and this lifespan extension is not additive with CR. DN-Dmp53-dependent lifespan extension is accompanied by reduction of Drosophila insulin-like peptide 2 (dILP2) mRNA levels and reduced insulin signaling (IIS) in the fat body, which suggests that Dmp53 may affect lifespan by modulating insulin signaling in the fly.
Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02903, USA.
Johannes H
JH
Bauer
Chengyi
C
Chang
Siti Nur Sarah
SN
Morris
Suzanne
S
Hozier
Sandra
S
Andersen
Joshua S
JS
Waitzman
Stephen L
SL
Helfand
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D017931:DNA Primers; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D002149:Energy Intake; D005799:Genes, Dominant; D007328:Insulin / Q000378:metabolism*; D008017:Life Expectancy; D015398:Signal Transduction / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D017931:DNA Primers; D029721:Drosophila Proteins; D007328:Insulin; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila