Kyle D Shead, Veneta Salyahetdinova, George S Baillie
{"title":"描绘丝胺 A 翻译后修饰的重要性。","authors":"Kyle D Shead, Veneta Salyahetdinova, George S Baillie","doi":"10.1042/BCJ20240121","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346442/pdf/","citationCount":"0","resultStr":"{\"title\":\"Charting the importance of filamin A posttranslational modifications.\",\"authors\":\"Kyle D Shead, Veneta Salyahetdinova, George S Baillie\",\"doi\":\"10.1042/BCJ20240121\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":8825,\"journal\":{\"name\":\"Biochemical Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346442/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1042/BCJ20240121\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical Journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1042/BCJ20240121","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
丝胶 A 是细胞细胞骨架中的一种重要蛋白质,因为它具有肌动蛋白结合特性和独特的同源二聚体杆状结构,能将肌动蛋白组织成三维正交网络,对细胞的运动、扩散和粘附至关重要。丝胶蛋白 A 受到广泛的翻译后修饰 (PTM),这有助于协调细胞结构,调节其庞大的蛋白-蛋白相互作用网络,而这正是丝胶蛋白发挥细胞信号枢纽作用的关键所在。已确定的 PTM 包括磷酸化、不可逆裂解、泛素介导的降解、羟基化和 O-GlcNAcylation,还有酪氨酸化、羰基化和乙酰化的初步证据。这里将介绍每种修饰及其与丝胺 A 功能的关系。这些修饰通常在一系列疾病中异常应用,包括但不限于癌症、心血管疾病和神经系统疾病,我们将讨论具有新型治疗模式的靶向特异性 PTMs 概念。总之,我们的综述是专题性的 "一站式服务",有助于了解丝胺 A 在细胞稳态中的功能,并深入探讨各种修饰如何增加丝胺 A 的额外控制水平。
Charting the importance of filamin A posttranslational modifications.
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.
期刊介绍:
Exploring the molecular mechanisms that underpin key biological processes, the Biochemical Journal is a leading bioscience journal publishing high-impact scientific research papers and reviews on the latest advances and new mechanistic concepts in the fields of biochemistry, cellular biosciences and molecular biology.
The Journal and its Editorial Board are committed to publishing work that provides a significant advance to current understanding or mechanistic insights; studies that go beyond observational work using in vitro and/or in vivo approaches are welcomed.
Painless publishing:
All papers undergo a rigorous peer review process; however, the Editorial Board is committed to ensuring that, if revisions are recommended, extra experiments not necessary to the paper will not be asked for.
Areas covered in the journal include:
Cell biology
Chemical biology
Energy processes
Gene expression and regulation
Mechanisms of disease
Metabolism
Molecular structure and function
Plant biology
Signalling