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首页> 外文期刊>Skeletal Muscle >Retracted: MyoD-dependent regulation of NF-κB activity couples cell-cycle withdrawal to myogenic differentiation
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Retracted: MyoD-dependent regulation of NF-κB activity couples cell-cycle withdrawal to myogenic differentiation

机译：缩回：依赖于MyoD的NF-κB活性调节将细胞周期停滞与成肌分化相结合

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Background Mice lacking MyoD exhibit delayed skeletal muscle regeneration and markedly enhanced numbers of satellite cells. Myoblasts isolated from MyoD-/- myoblasts proliferate more rapidly than wild type myoblasts, display a dramatic delay in differentiation, and continue to incorporate BrdU after serum withdrawal. Methods Primary myoblasts isolated from wild type and MyoD-/- mutant mice were examined by microarray analysis and further characterized by cell and molecular experiments in cell culture. Results We found that NF-κB, a key regulator of cell-cycle withdrawal and differentiation, aberrantly maintains nuclear localization and transcriptional activity in MyoD-/- myoblasts. As a result, expression of cyclin D is maintained during serum withdrawal, inhibiting expression of muscle-specific genes and progression through the differentiation program. Sustained nuclear localization of cyclin E, and a concomitant increase in cdk2 activity maintains S-phase entry in MyoD-/- myoblasts even in the absence of mitogens. Importantly, this deficit was rescued by forced expression of IκBαSR, a non-degradable mutant of IκBα, indicating that inhibition of NF-κB is sufficient to induce terminal myogenic differentiation in the absence of MyoD. Conclusion MyoD-induced cytoplasmic relocalization of NF-κB is an essential step in linking cell-cycle withdrawal to the terminal differentiation of skeletal myoblasts. These results provide important insight into the unique functions of MyoD in regulating the switch from progenitor proliferation to terminal differentiation.
机译：背景缺乏MyoD的小鼠骨骼肌再生延迟，卫星细胞数量明显增加。从MyoD-/-成肌细胞分离的成肌细胞比野生型成肌细胞增殖更快，分化显着延迟，并且在撤离血清后继续掺入BrdU。方法对野生型和MyoD-/-突变型小鼠分离的原代成肌细胞进行微阵列分析，并通过细胞培养和分子实验进一步表征。结果我们发现，NF-κB是细胞周期退出和分化的关键调节因子，在MyoD-/-成肌细胞中异常维持了核定位和转录活性。结果，细胞周期蛋白D的表达在血清停药期间得以维持，从而抑制了肌肉特异性基因的表达以及通过分化程序的进展。持续的细胞周期蛋白E核定位以及cdk2活性的同时增加，即使在没有促细胞分裂剂的情况下，也能使MyoD-/-成肌细胞进入S期。重要的是，这种缺陷可以通过强制表达IκBα（一种不可降解的IκBα突变体）来挽救，这表明在没有MyoD的情况下，抑制NF-κB足以诱导终末肌原性分化。结论MyoD诱导的NF-κB胞质重定位是将细胞周期退出与骨骼肌成肌细胞终末分化联系起来的重要步骤。这些结果为了解MyoD在调节从祖细胞增殖到终末分化的转换中的独特功能提供了重要的见识。

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