Regulation of the cell cycle and centrosome biology by deubiquitylases.
Regulation of the cell cycle and centrosome biology by deubiquitylases.
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DOI：
10.1042/bst20170087
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发表时间：
2017-10-15
影响因子：
3.9
通讯作者：
Coulson JM
中科院分区：
文献类型：
--
作者：
Darling S;Fielding AB;Sabat-Pośpiech D;Prior IA;Coulson JM
蛋白质泛素化的翻译后修饰越来越被认为是一种高度复杂的密码，有助于调节不同的细胞过程。在人类中，一个由近100个脱泛素酶家族(DUB)组成的家族被分配到六个亚家族，其中许多DUB可以从蛋白质中去除泛素来逆转信号。个体DUB的作用已经在特定的细胞过程中被描绘出来，包括许多在疾病中调节失调的过程，特别是癌症。作为潜在的可药物酶，与疾病相关的DUB作为药物靶标越来越引起人们的兴趣。DUBS的生物学、结构和调控已经在其他地方得到了广泛的综述，所以我们在这里特别关注DUBS在哺乳动物细胞中调节细胞周期过程中的作用。超过四分之一的DUB，代表四个不同的家族，已经被证明在细胞周期的单向进展中通过特定的检查点，或者在DNA损伤反应和修复途径中发挥作用。我们对这些角色进行分类，并讨论具体的例子。中心体是细胞内主要的微管核中心，在细胞分裂过程中形成双极有丝分裂纺锤体起着关键作用，这是在子细胞之间准确划分遗传物质所必需的。为了实现这种有丝分裂的作用，中心体经历了一个与细胞分裂周期密切相关的复杂复制周期。在这里，我们还分类和讨论了与中心体复制或功能相关的DUB，包括中心体聚集，这是具有多余中心体的癌细胞特有的有丝分裂生存策略。
Post-translational modification of proteins by ubiquitylation is increasingly recognised as a highly complex code that contributes to the regulation of diverse cellular processes. In humans, a family of almost 100 deubiquitylase enzymes (DUBs) are assigned to six subfamilies and many of these DUBs can remove ubiquitin from proteins to reverse signals. Roles for individual DUBs have been delineated within specific cellular processes, including many that are dysregulated in diseases, particularly cancer. As potentially druggable enzymes, disease-associated DUBs are of increasing interest as pharmaceutical targets. The biology, structure and regulation of DUBs have been extensively reviewed elsewhere, so here we focus specifically on roles of DUBs in regulating cell cycle processes in mammalian cells. Over a quarter of all DUBs, representing four different families, have been shown to play roles either in the unidirectional progression of the cell cycle through specific checkpoints, or in the DNA damage response and repair pathways. We catalogue these roles and discuss specific examples. Centrosomes are the major microtubule nucleating centres within a cell and play a key role in forming the bipolar mitotic spindle required to accurately divide genetic material between daughter cells during cell division. To enable this mitotic role, centrosomes undergo a complex replication cycle that is intimately linked to the cell division cycle. Here, we also catalogue and discuss DUBs that have been linked to centrosome replication or function, including centrosome clustering, a mitotic survival strategy unique to cancer cells with supernumerary centrosomes.