Ubiquitin-Regulated Cell Proliferation and Cancer
Ubiquitin-Regulated Cell Proliferation and Cancer
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DOI：
10.1007/978-3-030-38266-7_1
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发表时间：
2020-01-01
期刊：
影响因子：
--
通讯作者：
Farras, Rosa
中科院分区：
文献类型：
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作者：
Perez-Benavente, Beatriz;Fathinajafabadi Nasresfahani, Alihamze;Farras, Rosa
泛素连接酶（Ubiquitin ligases，E3）通过识别、相互作用和泛素化等途径，在细胞增殖和分化等过程中发挥重要作用。形成的泛素链的类型决定了底物的命运。泛素化底物可以被蛋白酶体降解，显示改变的亚细胞定位，或者可以在它们与功能蛋白质复合物的相互作用上受到修饰。E3活性的失调经常在各种人类病理学中发现，包括癌症。抑癌蛋白的不合理或加速降解，或相反，癌蛋白的异常高积累，有助于细胞增殖和转化。蛋白质丰度的异常可能与改变E3酶对蛋白质的直接或间接识别的突变或泛素连接酶的表达或活性水平的改变有关。通过几个例子，我们在这里说明蛋白质泛素化参与细胞周期调控的分子机制的复杂性和多样性。我们将讨论蛋白酶体介导的泛素依赖性降解的作用，非蛋白水解泛素化在细胞周期进程中的作用，以及这种失调对细胞转化的后果。最后，我们将强调从这些研究中产生的治疗干预的新机会。
Ubiquitin ligases (E3) play a crucial role in the regulation of different cellular processes such as proliferation and differentiation via recognition, interaction, and ubiquitination of key cellular proteins in a spatial and temporal regulated manner. The type of ubiquitin chain formed determines the fate of the substrates. The ubiquitinated substrates can be degraded by the proteasome, display altered subcellular localization, or can suffer modifications on their interaction with functional protein complexes. Deregulation of E3 activities is frequently found in various human pathologies, including cancer. The illegitimated or accelerated degradation of oncosuppressive proteins or, inversely, the abnormally high accumulation of oncoproteins, contributes to cell proliferation and transformation. Anomalies in protein abundance may be related to mutations that alter the direct or indirect recognition of proteins by the E3 enzymes or alterations in the level of expression or activity of ubiquitin ligases. Through a few examples, we illustrate here the complexity and diversity of the molecular mechanisms related to protein ubiquitination involved in cell cycle regulation. We will discuss the role of ubiquitin-dependent degradation mediated by the proteasome, the role of non-proteolytic ubiquitination during cell cycle progression, and the consequences of this deregulation on cellular transformation. Finally, we will highlight the novel opportunities that arise from these studies for therapeutic intervention.