Chakraborty Joy, Basso Valentina, Ziviani Elena
Department of Biology, University of Padova, Via Ugo Bassi 58b, 35131, Padova, Italy.
Istituto IRCCS San Camillo, Lido di Venezia, Venezia,, Italy.
Biol Direct. 2017 Feb 21;12(1):6. doi: 10.1186/s13062-017-0176-3.
Mutations in the gene encoding for the E3 ubiquitin ligase Parkin are associated to a rare form of familiar autosomal recessive Parkinsonism. Despite decades of research on the Parkin protein, whose structure has been recently solved, little is known about the specific signalling pathways that lead to Parkin activation. Parkin activity spans from mitochondria quality control to tumor suppression and stress protection; it is thus tempting to hypothesize that the broad impact of Parkin on cellular physiology might be the result of different post translational modifications that can be controlled by balanced opposing events. Sequence alignment of Parkin from different species indicates high homology between domains across Parkin orthologs and identifies highly conserved amino acid residues that, if modified, impinge on Parkin functions. In this review, we summarize findings on post translational modifications that have been shown to affect Parkin activity and stability.
This article was reviewed by Prof. Dr. Konstanze F. Winklhofer and by Prof. Thomas Simmen. Both reviewers have been nominated by Professor Luca Pellegrini.
编码E3泛素连接酶帕金（Parkin）的基因突变与一种罕见的家族性常染色体隐性帕金森病有关。尽管对帕金蛋白已进行了数十年研究，其结构最近也已解析清楚，但对于导致帕金激活的具体信号通路仍知之甚少。帕金的活性涵盖线粒体质量控制、肿瘤抑制和应激保护等方面；因此很容易推测，帕金对细胞生理学的广泛影响可能是由不同的翻译后修饰导致的，这些修饰可由平衡的相反事件控制。来自不同物种的帕金序列比对表明，帕金直系同源物各结构域之间具有高度同源性，并鉴定出了高度保守的氨基酸残基，这些残基若发生修饰会影响帕金的功能。在本综述中，我们总结了已证明会影响帕金活性和稳定性的翻译后修饰的相关研究结果。
本文由康斯坦泽·F·温克霍费尔（Konstanze F. Winklhofer）教授和托马斯·西姆门（Thomas Simmen）教授审阅。两位审阅者均由卢卡·佩莱格里尼（Luca Pellegrini）教授提名。
