Department of Physiology, Neurobiology and Behavior, and University of California, Davis, California 95616, USA.
FASEB J. 2012 Jul;26(7):2986-99. doi: 10.1096/fj.12-204495. Epub 2012 Apr 16.
Deletion of muscle RING finger 1 (MuRF1), an E3 ubiquitin ligase, leads to sparing of muscle mass following denervation. The purpose of this study was to test the hypothesis that muscle sparing in mice with a deletion of MuRF1 is due to the selective inhibition of the ubiquitin proteasome system. Activities of the 20S and 26S proteasomes, calpain and cathepsin L, were measured in the triceps surae muscles of wild-type (WT) and MuRF1-knockout (KO) mice at 3 and 14 d following denervation. In addition, fractional protein synthesis rates and differential gene expression were measured in WT and KO muscle. The major finding was that 20S and 26S proteasome activities were significantly elevated (1.5- to 2.5-fold) after 14 d of denervation in both WT and KO mice relative to control, but interestingly, the activities of both the 20S and 26S proteasome were significantly higher in KO than WT mice. Further, mRNA expression of MAFbx was elevated after 14 d of denervation in KO, but not WT, mice. These data challenge the conventional dogma that MuRF1 is controlling the degradation of only contractile proteins and suggest a role for MuRF1 in the global control of the ubiquitin proteasome system and protein turnover.
肌环指蛋白 1（MuRF1）的缺失，一种 E3 泛素连接酶，可导致去神经后肌肉质量得以保留。本研究旨在验证以下假设：MuRF1 缺失的小鼠肌肉得以保留是由于泛素蛋白酶体系统的选择性抑制。在去神经后 3 天和 14 天，分别测量野生型（WT）和 MuRF1 敲除（KO）小鼠比目鱼肌中的 20S 和 26S 蛋白酶体、钙蛋白酶和组织蛋白酶 L 的活性。此外，还测量了 WT 和 KO 肌肉中的蛋白合成率和差异基因表达。主要发现是，与对照组相比，WT 和 KO 小鼠去神经 14 天后，20S 和 26S 蛋白酶体的活性均显著升高（1.5-2.5 倍），但有趣的是，KO 小鼠的 20S 和 26S 蛋白酶体活性均显著高于 WT 小鼠。此外，KO 小鼠去神经 14 天后，MAFbx 的 mRNA 表达升高，但 WT 小鼠则没有。这些数据挑战了 MuRF1 仅控制收缩蛋白降解的传统观点，并表明 MuRF1 在泛素蛋白酶体系统和蛋白质周转的全局控制中发挥作用。
