Abstract：
Membrane-associated RING-CH (MARCH) E3 ubiquitin ligases, a family of RING-type E3 ubiquitin ligases, have garnered increased attention for their indispensable roles in immune regulation, inflammation, mitochondrial dynamics, and lipid metabolism. The MARCH E3 ligase family consists of eleven distinct members, and the dysregulation of many of these members has been documented in several human malignancies. Over the past two decades, extensive research has revealed that MARCH E3 ligases play pivotal roles in cancer progression by ubiquitinating key oncogenes and tumor suppressors and orchestrating various signaling pathways. Some MARCH E3s act as oncogenes, while others act as tumor suppressors, and the majority of MARCH E3s play both oncogenic and tumor suppressive roles in a context-dependent manner. Notably, there is special emphasis on the sole mitochondrial MARCH E3 ligase MARCH5, which regulates mitochondrial homeostasis within cancer cells. In this review, we delve into the diverse functions of MARCH E3 ligases across different cancer types, shedding light on the underlying molecular mechanisms mediating their effects, their regulatory effects on cancer and their potential as therapeutic targets.
摘要：
膜相关环-CH(MARCH)E3泛素连接酶，一个环型E3泛素连接酶家族，它们在免疫调节中不可或缺的作用引起了越来越多的关注，炎症,线粒体动力学，和脂质代谢。MARCHE3连接酶家族由11个不同的成员组成，并且在几种人类恶性肿瘤中已经记录了许多这些成员的失调。在过去的二十年里，广泛的研究表明,MARCHE3连接酶通过使关键癌基因和肿瘤抑制因子泛素化并协调各种信号通路在癌症进展中发挥关键作用.一些MARCHE3作为致癌基因，而其他人则充当肿瘤抑制因子，并且大多数MARCHE3以环境依赖性方式同时发挥致癌和肿瘤抑制作用。值得注意的是,特别强调唯一的线粒体MARCHE3连接酶MARCH5，它调节癌细胞内的线粒体稳态。在这次审查中,我们深入研究了MARCHE3连接酶在不同癌症类型中的不同功能，揭示介导它们作用的潜在分子机制，它们对癌症的调节作用及其作为治疗靶点的潜力。
