Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling
Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling
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DOI：
10.1073/pnas.0706121104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Helfand, Stephen L.
中科院分区：
文献类型：
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作者：
Bauer, Johannes H.;Chang, Chengyi;Helfand, Stephen L.
在黑腹果蝇中，p53（Dmp 53）是长寿的重要调节因子。Dmp 53在成年神经元中的显性阴性（DIN）形式的表达，而不是在肌肉或脂肪体细胞中的表达，延长了寿命。在神经系统中同时表达DN-Dmp 53并不能进一步延长卡路里限制的果蝇的寿命，这表明Dmp 53活性的降低可能是果蝇CR寿命延长途径的一部分。在这份报告中，我们表明，选择性表达DN-Dmp 53只有14胰岛素产生细胞（IPC）在大脑中延长寿命的程度相同的表达在所有神经元和这种寿命延长是不加CR。DN-Dmp 53依赖性寿命延长伴随着果蝇胰岛素样肽2（dILP 2）mRNA水平的降低和脂肪体中胰岛素信号（IIS）的减少，这表明Dmp 53可能通过调节果蝇中的胰岛素信号来影响寿命。
in Drosophila melanogaster, p53 (Dmp53) is an important mediator of longevity. Expression of dominant-negative (DIN) 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-extencling 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 pepticle 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.