Filamin A is an essential protein in the cell cytoskeleton because of its actin binding properties and unique homodimer rod-shaped structure, which organises actin into three-dimensional orthogonal networks imperative to cell motility, spreading and adhesion. Filamin A is subject to extensive posttranslational modification (PTM) which serves to co-ordinate cellular architecture and to modulate its large protein-protein interaction network which is key to the protein's role as a cellular signalling hub. Characterised PTMs include phosphorylation, irreversible cleavage, ubiquitin mediated degradation, hydroxylation and O-GlcNAcylation, with preliminary evidence of tyrosylation, carbonylation and acetylation. Each modification and its relation to filamin A function will be described here. These modifications are often aberrantly applied in a range of diseases including, but not limited to, cancer, cardiovascular disease and neurological disease and we discuss the concept of target specific PTMs with novel therapeutic modalities. In summary, our review represents a topical ‘one-stop-shop’ that enables understanding of filamin A function in cell homeostasis and provides insight into how a variety of modifications add an extra level of Filamin A control.

中文翻译：

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绘制细丝蛋白 A 翻译后修饰的重要性


细丝蛋白 A 是细胞骨架中的重要蛋白质，因为它具有肌动蛋白结合特性和独特的同二聚体杆状结构，可将肌动蛋白组织成对细胞运动、扩散和粘附至关重要的三维正交网络。细丝蛋白 A 受到广泛的翻译后修饰 (PTM)，其作用是协调细胞结构并调节其大型蛋白质-蛋白质相互作用网络，这是该蛋白质作为细胞信号传导中枢的关键。表征的 PTM 包括磷酸化、不可逆切割、泛素介导的降解、羟基化和 O-GlcNAc 酰化，并有酪氨酸化、羰基化和乙酰化的初步证据。这里将描述每种修饰及其与细丝蛋白A功能的关系。这些修饰经常被异常地应用于一系列疾病，包括但不限于癌症、心血管疾病和神经系统疾病，我们讨论了具有新治疗方式的靶标特异性 PTM 的概念。总之，我们的综述代表了主题“一站式服务”，使人们能够了解细丝蛋白 A 在细胞稳态中的功能，并深入了解各种修饰如何增加细丝蛋白 A 的额外控制水平。