The E3 ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle
The E3 ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle
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DOI：
10.1016/j.cmet.2007.09.009
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发表时间：
2007-11-01
期刊：
影响因子：
29
通讯作者：
Glass, David J.
中科院分区：
文献类型：
--
作者：
Clarke, Brian A.;Drujan, Doreen;Glass, David J.
骨骼肌萎缩是地塞米松(DEX)等合成糖皮质激素治疗的副作用，是与皮质醇水平升高相关的恶病质综合征的标志。DEX处理可上调E3泛素连接酶MuRF1(肌肉环指蛋白1)的转录水平。经DEX处理的分化肌管会耗尽肌球蛋白重链蛋白(MYH)，而MYH在物理上与MuRF1相关。MYH的这种丢失可以通过抑制MuRF1的表达来阻止。当野生型和MuRF1(-/-)小鼠接受地塞米松治疗时，MuRF1(-/-)小鼠表现出相对较少的MYH。在体外，MuRF1被证明是MYH的E3泛素连接酶。这些数据确定了MYH在萎缩条件下被耗尽的机制，并证明了抑制单个E3连接酶MuRF1足以维持这一重要的肌瘤蛋白。
Skeletal muscle atrophy occurs as a side effect of treatment with synthetic glucocorticoids such as dexamethasone (DEX) and is a hallmark of cachectic syndromes associated with increased cortisol levels. The E3 ubiquitin ligase MuRF1 (muscle RING finger protein 1) is transcriptionally upregulated by DEX treatment. Differentiated myotubes treated with DEX undergo depletion of myosin heavy chain protein (MYH), which physically associates with MuRF1. This loss of MYH can be blocked by inhibition of MuRF1 expression. When wild-type and MuRF1(-/-) mice are treated with DEX, the MuRF1(-/-) animals exhibit a relative sparing of MYH. In vitro, MuRF1 is shown to function as an E3 ubiquitin ligase for MYH. These data identify the mechanism by which MYH is depleted under atrophy conditions and demonstrate that inhibition of a single E3 ligase, MuRF1, is sufficient to maintain this important sarcomeric protein.