Laboratory of Signal Transduction, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Republic of Korea.
Biochem Biophys Res Commun. 2019 Oct 29;519(1):29-34. doi: 10.1016/j.bbrc.2019.08.090. Epub 2019 Aug 29.
Non-steroidal anti-inflammatory drug activated gene-1 (NAG-1), also known as growth differentiation factor 15 (GDF15), is a TGF-β (transforming growth factor beta) superfamily protein with a distinctive secretion pathway. NAG-1 is associated with multiple diseases including cancer, wherein it plays a role in both pro- and anti-cancer activities. We previously reported that NAG-1 is translocated to different subcellular compartments and its activity depends on its localization. In this paper, we report that the transfection of a novel peptide corresponding to the nuclear localization signal (NLS) of NAG-1 blocks its translocation to the nucleus. Further, accumulation of NAG-1 in the cytoplasm decreased mitochondrial membrane potential, thus implying apoptosis induction as a consequence. Overall, our results indicate that the novel peptide derived from NAG-1 NLS sequence is a promising tool for enhancing the anti-tumorigenic activity of NAG-1.
非甾体抗炎药激活基因-1（NAG-1），也称为生长分化因子 15（GDF15），是 TGF-β（转化生长因子β）超家族蛋白，具有独特的分泌途径。NAG-1 与多种疾病相关，包括癌症，在癌症中，它发挥着促癌和抗癌的双重作用。我们之前的研究表明，NAG-1 可转移到不同的亚细胞隔室，其活性取决于其定位。在本文中，我们报告称，转染对应于 NAG-1 核定位信号（NLS）的新型肽可阻止其向核内转移。此外，NAG-1 在细胞质中的积累降低了线粒体膜电位，从而暗示了凋亡的诱导。总的来说，我们的结果表明，源自 NAG-1 NLS 序列的新型肽是增强 NAG-1 抗肿瘤活性的有前途的工具。
