Necdin: A Multi Functional Protein with Potential Tumor Suppressor Role?
Necdin: A Multi Functional Protein with Potential Tumor Suppressor Role?
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DOI：
10.1002/mc.20567
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发表时间：
2009-11-01
影响因子：
4.6
通讯作者：
Knowles, Margaret A.
中科院分区：
文献类型：
--
作者：
Chapman, Emma J.;Knowles, Margaret A.
Necdin（NDN）是黑色素瘤相关抗原（法师）蛋白家族的一员，其首先在通过用视黄酸处理诱导分化的胚胎癌来源的小鼠干细胞中被鉴定。人类基因定位于染色体15 q11。该印记区域与Prader-Willi综合征（PWS）的发病机制有关，PWS是一种神经发育障碍，其中NDN是通过缺失、母体单亲二体或易位而沉默的多个基因之一。由于这种关联，许多兴趣集中在NDN在神经元发育和分化中的作用。然而，相当多的研究已经确定了NDN的其他功能。综合这些研究表明，多效性蛋白具有不同的功能，其中一些可能与肿瘤发生有关。NDN的下调发生在癌细胞系和原发性肿瘤中，表明肿瘤抑制作用。我们的工作假设是，NDN是一个值得进一步研究的候选人，就潜在的肿瘤抑制作用。在这篇文章中，我们概述了大量的证据支持的假设，NDN具有多种功能，其中一些表明，它可能是一种肿瘤抑制剂。NDN在关键过程中的作用，如与p53和E2 F-1的相互作用，造血干细胞静止，转录抑制，血管生成，分化和与polycomb组基因BMI 1的相互作用进行了讨论。NDN作为肿瘤抑制因子的确认可能对PWS患者的监测具有意义，并可能提出一种新的癌症治疗靶点。(C)2009 Wiley-Liss，Inc.
Necdin (NDN), a member of the melanoma-associated antigen (MAGE) family of proteins was first identified in mouse stem cells of embryonal carcinoma origin induced to differentiate by treatment with retinoic acid. The human gene maps to chromosome 15q11. This imprinted region is implicated in the pathogenesis of Prader-Willi syndrome (PWS), a neurodevelopmental disorder, where NDN is one of multiple genes silenced by deletion, maternal uniparental disomy or translocation. Due to this association, much interest has focused on the role of NDN in neuronal development and differentiation. However, a considerable number of studies have identified additional functions of NDN. Taken together these studies suggest a pleiotropic protein with diverse functions some of which may be relevant to tumorigenesis. Downregulation of NDN occurs in carcinoma cell lines and primary tumors, suggesting a tumor suppressor role. Our working hypothesis is that NDN is a worthy candidate for further studies with regard to a potential tumor suppressor role. In this article we outline the considerable evidence supporting the hypothesis that NDN has multiple functions, some of which indicate that it could be a tumor suppressor. The roles of NDN in key processes such as interaction with p53 and E2F-1, hematopoietic stem cell quiescence, transcriptional repression, angiogenesis, differentiation and interaction with the polycomb group gene BMI1 are discussed. Confirmation of NDN as a tumor suppressor may have implications for monitoring of PWS patients and could present a novel cancer therapeutic target. (C) 2009 Wiley-Liss, Inc.