APLP1 promotes dFoxO-dependent cell death in Drosophila
APLP1 promotes dFoxO-dependent cell death in Drosophila
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DOI：
10.1007/s10495-015-1097-1
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发表时间：
2015-03
期刊：
影响因子：
7.2
通讯作者：
Xingjun Wang;Yeqing Ma;Yu Zhao;Yujun Chen;Yujia Hu;Changyan Chen;Y. Shao;L. Xue
中科院分区：
文献类型：
--
作者：
Xingjun Wang;Yeqing Ma;Yu Zhao;Yujun Chen;Yujia Hu;Changyan Chen;Y. Shao;L. Xue
淀粉样前体样蛋白-1 （APLP1）属于淀粉样前体蛋白家族，该家族还包括淀粉样前体蛋白（APP）和淀粉样前体样蛋白-2 （APLP2）。虽然这三种蛋白具有相似的结构，并通过α-、β-和γ-分泌酶进行相同的切割加工，但APLP1与APP和APLP2具有不同的亚细胞定位，因此在体内可能发挥不同的作用。APP与阿尔茨海默病的发病机制有关，目前已有大量的研究集中在APP上，但APLP1的功能在很大程度上仍然难以捉摸。在这里，我们报道了APLP1在果蝇中的表达诱导细胞死亡并产生翅膀和胸部的发育缺陷。APLP1的这种功能依赖于转录因子dFoxO，因为dFoxO的缺失消除了APLP1诱导的细胞死亡和成体缺陷。与此一致的是，APLP1上调了dFoxO靶基因-两个众所周知的促凋亡基因的转录。因此，本研究首次提供了活体证据，证明APLP1能够诱导细胞死亡，FoxO是APLP1活性的重要下游介质。
The amyloid precursor like protein-1 (APLP1) belongs to the amyloid precursor protein family that also includes the amyloid precursor protein (APP) and the amyloid precursor like protein-2 (APLP2). Though the three proteins share similar structures and undergo the same cleavage processing by α-, β- and γ-secretases, APLP1 shows divergent subcellular localization from that of APP and APLP2, and thus, may perform distinct roles in vivo. While extensive studies have been focused on APP, which is implicated in the pathogenesis of Alzheimer’s disease, the functions of APLP1 remain largely elusive. Here we report that the expression of APLP1 inDrosophilainduces cell death and produces developmental defects in wing and thorax. This function of APLP1 depends on the transcription factor dFoxO, as the depletion of dFoxO abrogates APLP1-induced cell death and adult defects. Consistently, APLP1 up-regulates the transcription of dFoxO targethidandreaper-two well known pro-apoptotic genes. Thus, the present study provides the first in vivo evidence that APLP1 is able to induce cell death, and that FoxO is a crucial downstream mediator of APLP1’s activity.