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Hsp60 Post-translational Modifications: Functional and Pathological Consequences.
Frontiers in Molecular Biosciences ( IF 5 ) Pub Date : 2020-04-24 , DOI: 10.3389/fmolb.2020.00095
Celeste Caruso Bavisotto 1, 2 , Giusi Alberti 1 , Alessandra Maria Vitale 1 , Letizia Paladino 1 , Claudia Campanella 1 , Francesca Rappa 1 , Magdalena Gorska 3 , Everly Conway de Macario 2, 4 , Francesco Cappello 1, 2 , Alberto J L Macario 2, 4 , Antonella Marino Gammazza 1
Affiliation  

Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The question is by what mechanism this protein can become multifaceted. Likely, one factor contributing to this diversity is post-translational modification (PTM). The amino acid sequence of Hsp60 contains many potential phosphorylation sites, and other PTMs are possible such as O-GlcNAcylation, nitration, acetylation, S-nitrosylation, citrullination, oxidation, and ubiquitination. The effect of some of these PTMs on Hsp60 functions have been examined, for instance phosphorylation has been implicated in sperm capacitation, docking of H2B and microtubule-associated proteins, mitochondrial dysfunction, tumor invasiveness, and delay or facilitation of apoptosis. Nitration was found to affect the stability of the mitochondrial permeability transition pore, to inhibit folding ability, and to perturb insulin secretion. Hyperacetylation was associated with mitochondrial failure; S-nitrosylation has an impact on mitochondrial stability and endothelial integrity; citrullination can be pro-apoptotic; oxidation has a role in the response to cellular injury and in cell migration; and ubiquitination regulates interaction with the ubiquitin-proteasome system. Future research ought to determine which PTM causes which variations in the Hsp60 molecular properties and functions, and which of them are pathogenic, causing chaperonopathies. This is an important topic considering the number of acquired Hsp60 chaperonopathies already cataloged, many of which are serious diseases without efficacious treatment.



中文翻译:

Hsp60翻译后修饰:功能和病理后果。

Hsp60是一种属于第I组伴侣蛋白的伴侣,通常在线粒体内发挥作用,其中与伴侣伴侣Hsp10共同维持蛋白质稳态。除了这种典型作用外,Hsp60还可以在线粒体之外发挥其他作用,例如在细胞质,浆细胞膜,细胞外空间和体液中。这些非规范功能包括参与炎症,自身免疫,致癌作用,细胞复制以及健康和疾病中的其他细胞事件。因此,Hsp60是具有多种细胞和组织位置及功能的多方面分子,值得注意的是,因为只有一个热休克蛋白60基因。问题是这种蛋白质可以通过什么机制变成多方面的。可能导致这种多样性的一个因素是翻译后修饰(PTM)。Hsp60的氨基酸序列包含许多潜在的磷酸化位点,其他PTM也可能,例如O-GlcNAcylation,硝化,乙酰化,S-亚硝基化,瓜氨酸化,氧化和泛素化。已经检查了其中一些PTM对Hsp60功能的影响,例如,磷酸化与精子获能,H2B和微管相关蛋白的对接,线粒体功能障碍,肿瘤侵袭性以及凋亡的延迟或促进有关。发现硝化作用会影响线粒体通透性过渡孔的稳定性,抑制折叠能力并扰动胰岛素分泌。过度乙酰化与线粒体衰竭有关。S-亚硝基化影响线粒体的稳定性和内皮完整性。瓜氨酸化可以促凋亡;氧化在对细胞损伤的反应和细胞迁移中起作用;泛素调节与泛素-蛋白酶体系统的相互作用。未来的研究应该确定哪种PTM引起Hsp60分子特性和功能的哪些变异,以及哪些是致病的,从而引起伴侣病。考虑到已经分类的获得性Hsp60伴侣病的数量,这是一个重要的话题,其中许多是没有有效治疗的严重疾病。氧化在对细胞损伤的反应和细胞迁移中起作用;泛素化调节与泛素-蛋白酶体系统的相互作用。未来的研究应该确定哪种PTM引起Hsp60分子特性和功能的哪些变异,以及哪些是致病的,从而引起伴侣病。考虑到已经分类的获得性Hsp60伴侣病的数量,这是一个重要的话题,其中许多是没有有效治疗的严重疾病。氧化在对细胞损伤的反应和细胞迁移中起作用;泛素化调节与泛素-蛋白酶体系统的相互作用。未来的研究应该确定哪种PTM引起Hsp60分子特性和功能的哪些变异,以及哪些是致病的,从而引起伴侣病。考虑到已经分类的获得性Hsp60伴侣病的数量,这是一个重要的话题,其中许多是没有有效治疗的严重疾病。

更新日期:2020-04-24
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