Wing Simon S
Dept. of Medicine, McGill University, Experimental Therapeutics and Metabolism Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Int J Biochem Cell Biol. 2016 Oct;79:462-468. doi: 10.1016/j.biocel.2016.07.028. Epub 2016 Jul 27.
The ubiquitin proteasome system is well recognized to be involved in mediating muscle atrophy in response to diverse catabolic conditions. To date, almost all of the genes that have been implicated are ubiquitin ligases. Although ubiquitination is modulated also by deubiquitinating enzymes, the roles of these enzymes in muscle wasting remains largely unexplored. In this article, the potential roles of deubiquitinating enzymes in regulating muscle size are discussed. This is followed by a review of the roles described for USP19, the deubiquitinating enzyme that has been most studied in muscle wasting. This enzyme is upregulated in muscle in many catabolic conditions and its inactivation leads to protection from muscle loss induced by stimuli that are common in many illnesses causing cachexia. It can regulate both protein synthesis and protein degradation as well as myogenesis, thereby modulating the key processes that control muscle mass. Roles for other deubiquitinating enzymes remain possible and to be explored.
泛素蛋白酶体系统在介导多种分解代谢条件下的肌肉萎缩过程中所起的作用已得到广泛认可。迄今为止，几乎所有涉及的基因都是泛素连接酶。虽然去泛素化酶也可调节泛素化过程，但这些酶在肌肉萎缩中的作用在很大程度上仍未得到充分探索。在本文中，我们讨论了去泛素化酶在调节肌肉大小方面的潜在作用。接下来，我们将回顾在肌肉萎缩研究中被研究最多的去泛素化酶USP19所发挥的作用。在许多分解代谢条件下，这种酶在肌肉中表达上调，其失活可保护肌肉免受多种导致恶病质的疾病中常见刺激所诱导的肌肉损失。它既能调节蛋白质合成和蛋白质降解，又能调节肌生成，从而调控控制肌肉质量的关键过程。其他去泛素化酶也可能发挥作用，有待进一步探索。
