A novel role of PRR14 in the regulation of skeletal myogenesis.
A novel role of PRR14 in the regulation of skeletal myogenesis.
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DOI：
10.1038/cddis.2015.103
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发表时间：
2015-04-23
影响因子：
9
通讯作者：
Yuan ZM
中科院分区：
文献类型：
--
作者：
Yang M;Yuan ZM
参与组织和维持核结构的基因，如SYNE1、SYNE2、TREM43、EMD和LMNA的失调经常与各种称为椎板病的疾病有关，这些疾病通常影响肌肉组织。PRR14蛋白最近被报道将异染色质拴在核膜上，但其功能在很大程度上仍不清楚。在这里，我们提出了几条证据，证明了PRR14在调节成肌细胞分化中的关键作用。我们发现Prr14在骨骼肌发生过程中表达上调。Prr14的表达下调抑制了C2C12的分化，而Prr14的过表达则促进了C2C12的分化。PRR14的促肌生活性可能与其支持细胞存活、维持层蛋白A/C的稳定性和结构有关。此外，PRR14通过与异染色质蛋白1α(Hp1α)结合来刺激MyoD的活性。这些结果支持PRR14通过支持核板结构和增强MyoD活性来促进骨骼肌发生的模型。
Dysregulation of genes involved in organizing and maintaining nuclear structures, such as SYNE1, SYNE2, TREM43, EMD and LMNA is frequently associated with diverse diseases termed laminopathies, which often affect the muscle tissue. The PRR14 protein was recently reported to tether heterochromatin to nuclear lamina but its function remains largely unknown. Here, we present several lines of evidence demonstrating a critical role of PRR14 in regulation of myoblast differentiation. We found that Prr14 expression was upregulated during skeletal myogenesis. Knockdown of Prr14 impeded, whereas overexpression of PRR14 enhanced C2C12 differentiation. The pro-myogenesis activity of PRR14 seemed to correlate with its ability to support cell survival and to maintain the stability and structure of lamin A/C. In addition, PRR14 stimulated the activity of MyoD via binding to heterochromatin protein 1 alpha (HP1α). The results altogether support a model in which PRR14 promotes skeletal myogenesis via supporting nuclear lamina structure and enhancing the activity of MyoD.