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.
Bauer
Johannes H
JH
Department of Molecular Biology, Cell Biology and Biochemistry, Division of Biology and Medicine, Brown University, Providence, RI 02903, USA.
Chang
Chengyi
C
Morris
Siti Nur Sarah
SN
Hozier
Suzanne
S
Andersen
Sandra
S
Waitzman
Joshua S
JS
Helfand
Stephen L
SL
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