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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Degradation of survival motor neuron (SMN) protein is mediated via the ubiquitin/proteasome pathway.
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Degradation of survival motor neuron (SMN) protein is mediated via the ubiquitin/proteasome pathway.

机译：生存运动神经元（SMN）蛋白的降解是通过泛素/蛋白酶体途径介导的。

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摘要

Homozygous deletion or mutation in the survival motor neuron (SMN)1 gene causes proximal spinal muscular atrophy (SMA), whereas SMN2 acts as a modifying gene that can influence the severity of SMA. It has been suggested that restoration of the SMN protein level in neuronal cells may prevent cell loss and may be helpful for treatment of SMA. Recent studies indicate that the ubiquitin/proteasome pathway is a major system for proteolysis of intracellular proteins. In this study, we investigate whether SMN protein is degraded via the ubiquitin/proteasome pathway. Primary fibroblasts were established from the skin biopsies of SMA patients and the effect of a proteasome inhibitor MG132 and lysosome inhibitor NH(4)Cl on SMN protein level was examined. We found that MG132, but not NH(4)Cl, significantly increased the amount and nuclear accumulation of SMN protein in SMA patient's fibroblasts. Immunoprecipitation/western blot analysis indicated that SMN protein was ubiquitinated in cells. In vitro protein ubiquitination assay also demonstrated that SMN protein could be conjugated with ubiquitin. Taken together, we have provided clear evidences that degradation of SMN protein is mediated via the ubiquitin/proteasome pathway and suggest that proteasome inhibitors may up-regulate SMN protein level and may be useful for the treatment of SMA.
机译：生存运动神经元（SMN）1基因的纯合缺失或突变会导致近端脊髓性肌萎缩症（SMA），而SMN2则是可影响SMA严重程度的修饰基因。已经提出，神经元细胞中SMN蛋白水平的恢复可以防止细胞丢失，并且可能有助于SMA的治疗。最近的研究表明，遍在蛋白/蛋白酶体途径是细胞内蛋白质蛋白水解的主要系统。在这项研究中，我们调查了SMN蛋白是否通过泛素/蛋白酶体途径降解。从SMA患者的皮肤活检中建立了原代成纤维细胞，并检测了蛋白酶体抑制剂MG132和溶酶体抑制剂NH（4）Cl对SMN蛋白水平的影响。我们发现，MG132，而不是NH（4）Cl，显着增加了SMA患者成纤维细胞中SMN蛋白的数量和核积累。免疫沉淀/蛋白质印迹分析表明SMN蛋白在细胞中泛素化。体外蛋白质泛素化测定还表明，SMN蛋白可以与泛素结合。综上所述，我们已经提供了明确的证据，表明SMN蛋白的降解是通过泛素/蛋白酶体途径介导的，并表明蛋白酶体抑制剂可能会上调SMN蛋白水平，并可能用于治疗SMA。

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