文章：

核蛋白和癌症

Nucleophosmin and cancer

原文发布日期：2006-07-01

DOI: 10.1038/nrc1885

类型: Review Article

开放获取: 否

要点：

1. Nucleophosmin (NPM, also known as B23) is a ubiquitously expressed nucleolar phosphoprotein that constantly shuttles between the nucleus and cytoplasm. NPM contains distinct functional domains through which it has many functions in the cell.
2. NPM is involved in cellular activities related to both proliferation and growth-suppression pathways. It participates in the process of ribosome biogenesis, and it controls genetic stability through the regulation of centrosome duplication. As a result, NPM overexpression correlates with uncontrolled cell growth and cellular transformation, whereas the disruption of NPM expression can cause genomic instability and centrosome amplification, which increases the risk of cellular transformation.
3. NPM is involved in the apoptotic response to stress and oncogenic stimuli (such as DNA damage and hypoxia), and it can modulate the activity and stability of crucial tumour-suppressor proteins such as p53.
4. Loss of NPM function leads to the destabilization and functional impairment of the ARF tumour-suppressor pathways, as NPM functions as a positive regulator of ARF protein stability.
5. NPM is implicated in human tumorigenesis. NPM is frequently overexpressed in solid tumours of a diverse histological origin, and genetic alterations that involve NPM1 occur frequently in haematopoietic tumours, such as chromosomal translocations in both lymphoid and myeloid disorders, and mutations in acute myeloid leukaemia (AML).
6. In tumour cells where NPM1 has been altered, NPM function can potentially be impaired both by the presence of antagonizing mutated products hetero-dimerizing with the wild-type protein, and by the reduction in the dosage of the gene to a single functional allele.
7. Depending on its expression levels and gene dosage, NPM seems to function as either an oncogene or a tumour suppressor. Either partial functional loss or aberrant overexpression could lead to neoplastic transformation through distinct mechanisms.

要点翻译：

1. 核磷蛋白（NPM，亦称B23）是一种广泛表达的核仁磷蛋白，持续在细胞核与细胞质之间穿梭。NPM通过其独特的功能结构域在细胞内发挥多种作用。
2. 该蛋白参与细胞增殖和生长抑制通路的相关活动，既介入核糖体生物合成过程，又通过调控中心体复制维持遗传稳定性。因此，NPM过表达与细胞生长失控及细胞转化相关，而其表达紊乱会导致基因组不稳定性和中心体扩增，从而增加细胞转化风险。
3. NPM参与细胞应对应激和致癌刺激（如DNA损伤与缺氧）的凋亡反应，并能调节p53等关键抑癌蛋白的活性与稳定性。
4. 当NPM功能缺失时，由于其对ARF蛋白稳定性具有正向调控作用，ARF抑癌通路会出现功能紊乱和稳定性下降。
5. NPM与人类肿瘤发生密切相关：在多种组织学来源的实体瘤中常出现过表达，而NPM1基因改变常见于造血系统肿瘤，如淋巴系和髓系疾病中的染色体易位，以及急性髓系白血病（AML）中的基因突变。
6. 在NPM1发生改变的肿瘤细胞中，其功能可能通过两种机制受损：突变产物与野生型蛋白形成异源二聚体产生拮抗作用，或基因剂量减少至单个功能性等位基因水平。
7. 根据表达水平和基因剂量的不同，NPM可发挥癌基因或抑癌基因的功能。无论是部分功能缺失还是异常过表达，都可能通过不同机制导致肿瘤性转化。

英文摘要：

NPM1 is a crucial gene to consider in the context of the genetics and biology of cancer. NPM1 is frequently overexpressed, mutated, rearranged and deleted in human cancer. Traditionally regarded as a tumour marker and a putative proto-oncogene, it has now also been attributed with tumour-suppressor functions. Therefore, NPM can contribute to oncogenesis through many mechanisms. The aim of this review is to analyse the role of NPM in cancer, and examine how deregulated NPM activity (either gain or loss of function) can contribute to tumorigenesis.

摘要翻译： 

NPM1 是研究癌症遗传学与生物学时必须关注的关键基因。在人类肿瘤中，NPM1 常出现高表达、突变、重排及缺失。传统上它被视为肿瘤标志物和潜在的原癌基因，如今也被认为具有抑癌功能。因此，NPM 可通过多种机制参与肿瘤发生。本文旨在分析 NPM 在癌症中的作用，并探讨其活性失调（功能获得或丧失）如何促进肿瘤形成。

原文链接：

Nucleophosmin and cancer