Insights into the role and regulation of TCTP in skeletal muscle.
Insights into the role and regulation of TCTP in skeletal muscle.
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DOI：
10.18632/oncotarget.13009
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发表时间：
2017-03-21
期刊：
影响因子：
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通讯作者：
Hornberger TA
中科院分区：
文献类型：
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作者：
Goodman CA;Coenen AM;Frey JW;You JS;Barker RG;Frankish BP;Murphy RM;Hornberger TA
免疫控制肿瘤蛋白（TCTP）在一系列癌细胞类型中上调，部分是通过激活雷帕霉素（mTOR）的机制靶点。最近，TCTP也被提出作为mTOR的间接激活剂。虽然已知mTOR在骨骼肌质量的调节中起主要作用，但关于TCTP在该有丝分裂后组织中的作用和调节知之甚少。这项研究表明，肌肉TCTP和mTOR信号转导在一系列小鼠模型（mdx小鼠，机械负荷诱导的肥大，去神经支配和固定诱导的萎缩）中上调。此外，在肥大和萎缩条件下观察到的TCTP增加部分通过雷帕霉素敏感性mTOR依赖性机制发生。然而，TCTP的过表达不足以激活mTOR信号传导（或增加蛋白质合成），因此不太可能参与最近提出的与mTOR的正反馈回路。然而，TCTP过度表达足以诱导肌纤维肥大。最后，TCTP过表达抑制了肌肉特异性泛素蛋白酶体E3连接酶MuRF1的启动子活性，表明TCTP可能在抑制蛋白质降解中发挥作用。这些发现提供了新的数据TCTP在体内骨骼肌中的作用和调节。
The translationally controlled tumor protein (TCTP) is upregulated in a range of cancer cell types, in part, by the activation of the mechanistic target of rapamycin (mTOR). Recently, TCTP has also been proposed to act as an indirect activator of mTOR. While it is known that mTOR plays a major role in the regulation of skeletal muscle mass, very little is known about the role and regulation of TCTP in this post-mitotic tissue. This study shows that muscle TCTP and mTOR signaling are upregulated in a range of mouse models (mdx mouse, mechanical load-induced hypertrophy, and denervation- and immobilization-induced atrophy). Furthermore, the increase in TCTP observed in the hypertrophic and atrophic conditions occurred, in part, via a rapamycin-sensitive mTOR-dependent mechanism. However, the overexpression of TCTP was not sufficient to activate mTOR signaling (or increase protein synthesis) and is thus unlikely to take part in a recently proposed positive feedback loop with mTOR. Nonetheless, TCTP overexpression was sufficient to induce muscle fiber hypertrophy. Finally, TCTP overexpression inhibited the promoter activity of the muscle-specific ubiquitin proteasome E3-ligase, MuRF1, suggesting that TCTP may play a role in inhibiting protein degradation. These findings provide novel data on the role and regulation of TCTP in skeletal muscle in vivo.