Kandala Sridhar, Kim Il-Man, Su Huabo
Vascular Biology Center, Medical College of Georgia, Georgia Regents University Augusta, GA, USA.
Vascular Biology Center, Medical College of Georgia, Georgia Regents University Augusta, GA, USA ; Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University Augusta, GA, USA.
Am J Cardiovasc Dis. 2014 Dec 29;4(4):140-58. eCollection 2014.
Neddylation is a post-translational protein modification that conjugates a ubiquitin-like protein NEDD8 to target proteins. Similar to ubiquitination, neddylation is mediated by a cascade of three NEDD8 specific enzymes, an E1 activating enzyme, an E2 conjugating enzyme and one of the several E3 ligases. Neddylation is countered by the action of deneddylases via a process termed deneddylation. By altering the substrate's conformation, stability, subcellular localization or binding affinity to DNA or proteins, neddylation regulates diverse cellular processes including the ubiquitin-proteasome system-mediated protein degradation, protein transcription, cell signaling etc. Dysregulation of neddylation has been linked to cancer, neurodegenerative disorders, and more recently, cardiac disease. Here we comprehensively overview the biochemistry, the proteome and the biological function of neddylation. We also summarize the recent progress in revealing the physiological and pathological role of neddylation and deneddylation in the heart.
Neddylation是一种蛋白质翻译后修饰，它将一种类泛素蛋白NEDD8与靶蛋白结合。与泛素化类似，Neddylation由一系列三种NEDD8特异性酶介导，一种E1激活酶、一种E2缀合酶和几种E3连接酶之一。去Neddylation酶的作用通过一个称为去Neddylation的过程来对抗Neddylation。通过改变底物的构象、稳定性、亚细胞定位或与DNA或蛋白质的结合亲和力，Neddylation调节多种细胞过程，包括泛素-蛋白酶体系统介导的蛋白质降解、蛋白质转录、细胞信号传导等。Neddylation的失调与癌症、神经退行性疾病以及最近的心脏病有关。在这里，我们全面概述了Neddylation的生物化学、蛋白质组和生物学功能。我们还总结了揭示Neddylation和去Neddylation在心脏中的生理和病理作用的最新进展。
