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果蝇中 Notch 信号通路的调控:异质核核糖核蛋白 Hrp48 和 Deltex 的作用。

Regulation of Notch Signaling in Drosophila melanogaster: The Role of the Heterogeneous Nuclear Ribonucleoprotein Hrp48 and Deltex.

机构信息

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

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

出版信息

Adv Exp Med Biol. 2020;1227:95-105. doi: 10.1007/978-3-030-36422-9_7.

Abstract

Notch signaling is an evolutionarily conserved pathway that plays a central role in a number of cellular events during metazoan development. Due to its involvement in numerous developmental events, Notch signaling requires tight spatial and temporal regulation. Deltex is a cytoplasmic protein that physically binds to the Notch and regulates its signaling activity in a context-dependent manner. However, the biology of Deltex in regulation of Notch signaling is not well explored. For a better understanding of Deltex activity in the regulatory circuit of Notch pathway, a co-IP-based screening was performed. Hrp48, an RNA-binding protein, was identified as an interacting partner of Deltex in that screening. Interaction of these two proteins seemed to regulate the Notch signaling outcome in the epithelial tissue. Additionally, it was found that coexpression of Deltex and Hrp48 can lead to cell death as well as JNK activation. Considering the fact of well conserved nature of Notch as well as both of these two proteins, namely, Hrp48 and Deltex, this interaction can be helpful to understand the regulation of Notch signaling both in development and disease condition.

摘要

Notch 信号通路是一种进化上保守的途径,在后生动物发育过程中的许多细胞事件中发挥核心作用。由于 Notch 信号通路参与了许多发育事件,因此需要严格的时空调节。Deltex 是一种细胞质蛋白,它以依赖于上下文的方式与 Notch 结合并调节其信号活性。然而,Deltex 在 Notch 信号通路调控中的生物学功能尚未得到充分探索。为了更好地理解 Deltex 在 Notch 途径调控回路中的活性,进行了基于 co-IP 的筛选。在该筛选中,Hrp48,一种 RNA 结合蛋白,被鉴定为 Deltex 的相互作用伙伴。这两种蛋白质的相互作用似乎调节了上皮组织中的 Notch 信号转导结果。此外,还发现 Deltex 和 Hrp48 的共表达会导致细胞死亡和 JNK 激活。考虑到 Notch 以及这两种蛋白质(即 Hrp48 和 Deltex)的高度保守性质,这种相互作用有助于理解 Notch 信号在发育和疾病状态下的调控。

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