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端锚聚合酶通过激活果蝇中的 JNK 信号来调节细胞凋亡。

Tankyrase regulates apoptosis by activating JNK signaling in Drosophila.

机构信息

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou, Zhejiang, China.

School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou, Zhejiang, China; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

出版信息

Biochem Biophys Res Commun. 2018 Sep 18;503(4):2234-2239. doi: 10.1016/j.bbrc.2018.06.143. Epub 2018 Jul 9.

Abstract

Programmed cell death (PCD), or apoptosis, plays essential roles in various cellular and developmental processes, and dysregulation of apoptosis causes many diseases. Thus, regulation of apoptotic process is very important. Drosophila tankyrase (DTNKS) is an evolutionarily conserved protein with poly(ADP-ribose) polymerase activity. In mammalian cells, tankyrases (TNKSs) have been reported to regulate cell death. To determine whether DTNKS plays function in inducing apoptosis in in vivo development, we used Drosophila as a model system and generated transgenic flies expressing DTNKS. We show that ectopic expression of DTNKS promotes caspase-dependent apoptosis and knockdown of DTNKS by RNAi dramatically alleviates apoptotic defect caused by ectopic expression of pro-apoptotic protein hid or rpr in the adult eye. Moreover, our result shows that ectopic expression of DTNKS triggers the activation of c-Jun N-terminal kinase (JNK) signaling, which is required for DTNKS-mediated apoptosis. Taken together, our finding identifies the role of DTNKS in regulating apoptosis by activating JNK signaling in Drosophila.

摘要

程序性细胞死亡(PCD)或细胞凋亡在各种细胞和发育过程中起着至关重要的作用,凋亡的失调会导致许多疾病。因此,调节凋亡过程非常重要。果蝇 Tankyrase(DTNKS)是一种具有多聚(ADP-核糖)聚合酶活性的进化保守蛋白。在哺乳动物细胞中,已报道 Tankyrases(TNKSs)调节细胞死亡。为了确定 DTNKS 是否在体内发育过程中诱导细胞凋亡中发挥作用,我们使用果蝇作为模型系统,并生成了表达 DTNKS 的转基因果蝇。我们发现 DTNKS 的异位表达促进了半胱天冬酶依赖性细胞凋亡,并且通过 RNAi 敲低 DTNKS 可显著减轻凋亡缺陷,这种凋亡缺陷是由凋亡蛋白 hid 或 rpr 的异位表达在成年果蝇眼睛中引起的。此外,我们的结果表明,DTNKS 的异位表达触发了 c-Jun N-末端激酶(JNK)信号的激活,这是 DTNKS 介导的细胞凋亡所必需的。总之,我们的发现确定了 DTNKS 通过在果蝇中激活 JNK 信号来调节凋亡的作用。

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