Center for Advanced Studies and Technology (CAST), University of Chieti "G. d'Annunzio", Via Polacchi, 66100 Chieti, Italy.
Department of Medical, Oral and Biotechnological Sciences, University of Chieti "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
Int J Mol Sci. 2020 Jul 10;21(14):4885. doi: 10.3390/ijms21144885.
Nucleophosmin (NPM1) is a mainly nucleolar protein that shuttles between nucleoli, nucleoplasm and cytoplasm to fulfill its many functions. It is a chaperone of both nucleic acids and proteins and plays a role in cell cycle control, centrosome duplication, ribosome maturation and export, as well as the cellular response to a variety of stress stimuli. NPM1 is a hub protein in nucleoli where it contributes to nucleolar organization through heterotypic and homotypic interactions. Furthermore, several alterations, including overexpression, chromosomal translocations and mutations are present in solid and hematological cancers. Recently, novel germline mutations that cause dyskeratosis congenita have also been described. This review focuses on NPM1 interactions and inhibition. Indeed, the list of NPM1 binding partners is ever-growing and, in recent years, many studies contributed to clarifying the structural basis for NPM1 recognition of both nucleic acids and several proteins. Intriguingly, a number of natural and synthetic ligands that interfere with NPM1 interactions have also been reported. The possible role of NPM1 inhibitors in the treatment of multiple cancers and other pathologies is emerging as a new therapeutic strategy.
核仁磷酸蛋白（Nucleophosmin，NPM1）是一种主要定位于核仁的蛋白，它在核仁、核质和细胞质之间穿梭，以发挥其多种功能。它是核酸和蛋白质的伴侣，在细胞周期调控、中心体复制、核糖体成熟和输出以及细胞对各种应激刺激的反应中发挥作用。NPM1 是核仁的一个枢纽蛋白，通过异质和同质相互作用有助于核仁的组织。此外，在实体瘤和血液系统恶性肿瘤中存在多种改变，包括过表达、染色体易位和突变。最近，还描述了导致先天性角化不良的种系突变。这篇综述重点关注 NPM1 的相互作用和抑制。事实上，NPM1 的结合伙伴列表不断增加，近年来，许多研究有助于阐明 NPM1 识别核酸和几种蛋白质的结构基础。有趣的是，已经报道了许多天然和合成的配体，它们可以干扰 NPM1 的相互作用。NPM1 抑制剂在治疗多种癌症和其他疾病中的可能作用正在成为一种新的治疗策略。
