Cancer is a leading cause of death worldwide, resulting in ∼10 million deaths in 2020. Major oncogenic effectors are the Myc proto-oncogene family, which consists of three members including c-Myc, N-Myc, and L-Myc. As a pertinent example of the role of the Myc family in tumorigenesis, amplification of MYCN in childhood neuroblastoma strongly correlates with poor patient prognosis. Complexes between Myc oncoproteins and their partners such as hypoxia-inducible factor-1α and Myc-associated protein X (MAX) result in proliferation arrest and pro-proliferative effects, respectively. Interactions with other proteins are also important for N-Myc activity. For instance, the enhancer of zest homolog 2 (EZH2) binds directly to N-Myc to stabilize it by acting as a competitor against the ubiquitin ligase, SCFFBXW7, which prevents proteasomal degradation. Heat shock protein 90 may also be involved in N-Myc stabilization since it binds to EZH2 and prevents its degradation. N-Myc downstream-regulated gene 1 (NDRG1) is downregulated by N-Myc and participates in the regulation of cellular proliferation via associating with other proteins, such as glycogen synthase kinase-3β and low-density lipoprotein receptor-related protein 6. These molecular interactions provide a better understanding of the biologic roles of N-Myc and NDRG1, which can be potentially used as therapeutic targets. In addition to directly targeting these proteins, disrupting their key interactions may also be a promising strategy for anti-cancer drug development. This review examines the interactions between the Myc proteins and other molecules, with a special focus on the relationship between N-Myc and NDRG1 and possible therapeutic interventions. SIGNIFICANCE STATEMENT: Neuroblastoma is one of the most common childhood solid tumors, with a dismal five-year survival rate. This problem makes it imperative to discover new and more effective therapeutics. The molecular interactions between major oncogenic drivers of the Myc family and other key proteins; for example, the metastasis suppressor, NDRG1, may potentially be used as targets for anti-neuroblastoma drug development. In addition to directly targeting these proteins, disrupting their key molecular interactions may also be promising for drug discovery.

中文翻译：

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Myc 家族和转移抑制剂 NDRG1：通过创新疗法瞄准关键分子相互作用。

癌症是全球主要死亡原因，2020 年将导致约 1000 万人死亡。主要的致癌效应子是 Myc 原癌基因家族，由三个成员组成，包括 c-Myc、N-Myc 和 L-Myc。作为 Myc 家族在肿瘤发生中的作用的一个相关例子，儿童神经母细胞瘤中 MYCN 的扩增与患者不良预后密切相关。Myc 癌蛋白与其伙伴（例如缺氧诱导因子 1α 和 Myc 相关蛋白 X (MAX)）之间的复合物分别导致增殖停滞和促增殖作用。与其他蛋白质的相互作用对于 N-Myc 活性也很重要。例如，zest 同源物 2 (EZH2) 的增强子直接与 N-Myc 结合，通过充当泛素连接酶 SCFFBXW7 的竞争者来稳定 N-Myc，从而防止蛋白酶体降解。热休克蛋白 90 也可能参与 N-Myc 稳定，因为它与 EZH2 结合并防止其降解。N-Myc 下游调节基因 1 (NDRG1) 被 N-Myc 下调，并通过与其他蛋白质（如糖原合成酶激酶 3β 和低密度脂蛋白受体相关蛋白 6）结合参与细胞增殖的调节。分子相互作用有助于更好地理解 N-Myc 和 NDRG1 的生物学作用，它们可以作为潜在的治疗靶点。除了直接靶向这些蛋白质之外，破坏它们的关键相互作用也可能是抗癌药物开发的一个有前途的策略。这篇综述研究了 Myc 蛋白与其他分子之间的相互作用，特别关注 N-Myc 和 NDRG1 之间的关系以及可能的治疗干预措施。意义声明：神经母细胞瘤是最常见的儿童实体瘤之一，五年生存率很低。这个问题使得发现新的、更有效的治疗方法势在必行。Myc 家族主要致癌驱动因素与其他关键蛋白之间的分子相互作用；例如，转移抑制因子 NDRG1 可能用作抗神经母细胞瘤药物开发的靶点。除了直接靶向这些蛋白质之外，破坏它们的关键分子相互作用也可能有利于药物发现。