Department of Medicine (Cardiology Division), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Trends Mol Med. 2013 Apr;19(4):239-49. doi: 10.1016/j.molmed.2013.01.005. Epub 2013 Feb 27.
Regulated protein degradation through the ubiquitin-proteasome and lysosomal/autophagy systems is critical for homeostatic protein turnover in cardiac muscle and for proper cardiac function. The discovery of muscle-specific components in these systems has illuminated how aberrations in their levels are pivotal to the development of cardiac stress and disease. New evidence suggests that equal importance in disease development should be given to ubiquitously expressed degradation components. These are compartmentalized within cardiac muscles and, when mislocalized, can be critical in the development of specific cardiac diseases. Here, we discuss how alterations in the compartmentalization of degradation components affect disease states, the tools available to investigate these mechanisms, as well as recent discoveries that highlight the therapeutic value of targeting these pathways in disease.
通过泛素-蛋白酶体和溶酶体/自噬系统对蛋白质进行调控性降解，对于心肌中蛋白质的动态平衡以及心脏功能的正常发挥非常重要。这些系统中肌肉特异性成分的发现阐明了它们水平的异常对心脏应激和疾病的发展具有关键作用。新的证据表明，在疾病发展中，普遍表达的降解成分同样重要。这些成分在心肌中进行区室化，当它们发生定位错误时，可能会在特定心脏疾病的发展中起关键作用。在这里，我们讨论了降解成分区室化的改变如何影响疾病状态，探讨这些机制的现有工具，以及最近的发现强调了靶向这些途径在疾病治疗中的价值。
