Alternative pathway of cell death in Drosophila mediated by NF-κB transcription factor Relish
Alternative pathway of cell death in Drosophila mediated by NF-κB transcription factor Relish
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DOI：
10.1073/pnas.1110666109
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发表时间：
2012-03-06
影响因子：
11.1
通讯作者：
Dolph, Patrick J.
中科院分区：
文献类型：
--
作者：
Chinchore, Yashodhan;Gerber, Gloria F.;Dolph, Patrick J.
光感受器细胞死亡伴随着许多视网膜变性疾病导致人类不可逆的视力丧失。然而，执行细胞死亡的精确分子途径尚不清楚。我们的研究结果从果蝇模型的视网膜变性证实了以前报道的结果，即发育凋亡途径不参与感光细胞的死亡。通过进行候选基因的方法，我们发现参与对革兰氏阴性细菌的免疫反应的参与者参与视网膜变性。在这里，我们报告说，NF-κ B B转录因子Relish调节神经元细胞死亡。视网膜变性是防止在遗传背景，阻止风味激活。我们还报告，N-末端域的Relish编码独特的毒性功能。这些数据揭示了果蝇视网膜变性的独特分子途径，并确定了NF-κ B信号传导在细胞死亡中的一个先前未知的功能。
Photoreceptor cell death accompanying many retinal degenerative disorders results in irreversible loss of vision in humans. However, the precise molecular pathway that executes cell death is not known. Our results from a Drosophila model of retinal degeneration corroborate previously reported findings that the developmental apoptotic pathway is not involved in photoreceptor cell demise. By undertaking a candidate gene approach, we find that players involved in the immune response against Gram-negative bacteria are involved in retinal degeneration. Here, we report that the NF-kappa B transcription factor Relish regulates neuronal cell death. Retinal degeneration is prevented in genetic backgrounds that block Relish activation. We also report that the N-terminal domain of Relish encodes unique toxic functions. These data uncover a unique molecular pathway of retinal degeneration in Drosophila and identify a previously unknown function of NF-kappa B signaling in cell death.