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德尔泰克斯与 Eiger 相互作用,从而影响黑腹果蝇的细胞死亡。

Deltex interacts with Eiger and consequently influences the cell death in Drosophila melanogaster.

机构信息

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.

出版信息

Cell Signal. 2018 Sep;49:17-29. doi: 10.1016/j.cellsig.2018.05.003. Epub 2018 May 15.

Abstract

TNF-JNK signaling is one of the highly conserved signaling pathways that regulate a broad spectrum of cellular processes including proliferation and apoptosis. Eiger, the sole homologue of TNF in Drosophila, initiates the TNF-JNK pathway to induce cell death. Previously, Deltex (Dx) has been identified as a Notch signaling component that regulates vesicular trafficking of Notch. In the present study, we have investigated the interaction between these two proteins in order to identify how Dx influences the activity of Eiger. Dx is found to act as a novel modulator of JNK-mediated cell death inducing activity of Eiger. Additionally, we observe that dx genetically interacts with eiger during wing development, and these two proteins, Dx and Eiger, colocalize in the cytoplasm. Our analysis reveals that Dx is involved in the cytoplasmic relocalization of Eiger from the cell membrane, thereby influencing Eiger-mediated JNK-activation process. Moreover, we demonstrate that Dx potentiates the activity of Eiger to downregulate Notch signaling pathway by retaining the Notch protein in the cytoplasm. Together, our findings reveal a novel role of Dx to modulate the signaling activity of Eiger and subsequent JNK-mediated cell death.

摘要

TNF-JNK 信号通路是高度保守的信号通路之一,调节包括增殖和凋亡在内的广泛的细胞过程。Eiger 是果蝇中 TNF 的唯一同源物,它启动 TNF-JNK 通路诱导细胞死亡。先前,Deltex (Dx) 已被鉴定为 Notch 信号通路的一个组成部分,调节 Notch 的囊泡运输。在本研究中,我们研究了这两种蛋白质之间的相互作用,以确定 Dx 如何影响 Eiger 的活性。研究发现,Dx 作为 Eiger 的 JNK 介导细胞死亡诱导活性的新型调节剂。此外,我们观察到 dx 在翼发育过程中与 eiger 发生遗传相互作用,并且这两种蛋白质 Dx 和 Eiger 在细胞质中共定位。我们的分析表明,Dx 参与了 Eiger 从细胞膜向细胞质的重新定位,从而影响 Eiger 介导的 JNK 激活过程。此外,我们证明 Dx 通过将 Notch 蛋白保留在细胞质中增强 Eiger 的活性以下调 Notch 信号通路。总之,我们的研究结果揭示了 Dx 调节 Eiger 的信号活性以及随后的 JNK 介导的细胞死亡的新作用。

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