During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation.
During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation.
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DOI：
10.1083/jcb.200901052
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Goldberg AL
中科院分区：
文献类型：
--
作者：
Cohen S;Brault JJ;Gygi SP;Glass DJ;Valenzuela DM;Gartner C;Latres E;Goldberg AL
肌原纤维蛋白的丧失是肌肉萎缩的标志。肌环指1 (MuRF1)，一种泛素连接酶，在萎缩过程中被显著诱导表达，MuRF1的缺失减轻了肌肉萎缩。我们产生了表达环缺失突变体MuRF1的小鼠，该突变体可以结合但不能泛素化底物。去神经支配肌肉中结合蛋白的质谱分析鉴定出许多肌原纤维成分。在去神经支配或禁食时，萎缩的肌肉表现为肌球蛋白结合蛋白C （MyBP-C）和肌球蛋白轻链1和2 （MyLC1和MyLC2）从肌原纤维中丢失，而肌球蛋白重链（MyHC）则没有任何可测量的减少。它们的选择性损失需要MuRF1。MyHC在肌原纤维中受相关蛋白的泛素化保护，但最终经历murf1依赖性降解。相反，MuRF1使MyBP-C、MyLC1和MyLC2泛素化，甚至在肌原纤维中也是如此。因为这些蛋白稳定了粗丝，它们的选择性泛素化可能促进粗丝的分解。然而，细丝成分减少的机制不需要MuRF1。
Loss of myofibrillar proteins is a hallmark of atrophying muscle. Expression of muscle RING-finger 1 (MuRF1), a ubiquitin ligase, is markedly induced during atrophy, and MuRF1 deletion attenuates muscle wasting. We generated mice expressing a Ring-deletion mutant MuRF1, which binds but cannot ubiquitylate substrates. Mass spectrometry of the bound proteins in denervated muscle identified many myofibrillar components. Upon denervation or fasting, atrophying muscles show a loss of myosin-binding protein C (MyBP-C) and myosin light chains 1 and 2 (MyLC1 and MyLC2) from the myofibril, before any measurable decrease in myosin heavy chain (MyHC). Their selective loss requires MuRF1. MyHC is protected from ubiquitylation in myofibrils by associated proteins, but eventually undergoes MuRF1-dependent degradation. In contrast, MuRF1 ubiquitylates MyBP-C, MyLC1, and MyLC2, even in myofibrils. Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1.
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影响因子：
64.5
作者：
Koegl, M;Hoppe, T;Jentsch, S
通讯作者：
Jentsch, S
影响因子：
10.8
作者：
Chen, Zhenyue;Huang, Wei;Xu, Xiaolei
通讯作者：
Xu, Xiaolei
影响因子：
3.5
作者：
Jang, JH
通讯作者：
Jang, JH
DOI：
10.1083/jcb.200108089
发表时间：
2002-04-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
McElhinny AS;Kakinuma K;Sorimachi H;Labeit S;Gregorio CC
通讯作者：
Gregorio CC
影响因子：
11.2
作者：
Kwak, KS;Zhou, XL;Han, HQ
通讯作者：
Han, HQ