Department of Pathology, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
FASEB J. 2010 Nov;24(11):4153-66. doi: 10.1096/fj.09-151464. Epub 2010 Jul 28.
The N-myc downstream regulated gene (NDRG) family of proteins consists of 4 members, NDRG1-4, which are well conserved through evolution. The first member to be discovered and responsible for the family name was NDRG1, because its expression is repressed by the proto-oncogenes MYCN and MYC. All family members are characterized by an α/β hydrolase-fold motif; however, the precise molecular and cellular function of these family members has not been fully elucidated. Although the exact function of NDRG family members has not been clearly elucidated, emerging evidence suggests that mutations in these genes are associated with diverse neurological and electrophysiological syndromes. In addition, aberrant expression as well as tumor suppressor and oncogenic functions affecting key hallmarks of carcinogenesis such as cell proliferation, differentiation, migration, invasion, and stress response have been reported for several of the NDRG proteins. In this review, we summarize the current literature on the NDRG family members concerning their structure, origin, and tissue distribution. In addition, we review the current knowledge regarding the regulation and signaling of the NDRG family members in development and normal physiology. Finally, their role in disease and potential clinical applications (their role as detection or prognostic markers) are discussed.
N- MYC 下游调节基因（NDRG）家族蛋白由 4 个成员组成，NDRG1-4，在进化过程中高度保守。第一个被发现并负责该家族名称的成员是 NDRG1，因为其表达受原癌基因 MYCN 和 MYC 的抑制。所有家族成员的特征是具有α/β水解酶折叠基序；然而，这些家族成员的确切分子和细胞功能尚未完全阐明。尽管 NDRG 家族成员的确切功能尚未明确阐明，但新出现的证据表明，这些基因的突变与多种神经和电生理综合征有关。此外，已经报道了几种 NDRG 蛋白的异常表达以及肿瘤抑制和致癌功能，这些功能影响着细胞增殖、分化、迁移、侵袭和应激反应等癌症发生的关键特征。在这篇综述中，我们总结了有关 NDRG 家族成员的结构、起源和组织分布的最新文献。此外，我们还综述了目前关于 NDRG 家族成员在发育和正常生理过程中的调节和信号转导的知识。最后，讨论了它们在疾病中的作用以及潜在的临床应用（作为检测或预后标志物的作用）。
