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PRR14在骨骼肌生成调节中的新作用。

A novel role of PRR14 in the regulation of skeletal myogenesis.

作者信息

Yang M, Yuan Z-M

机构信息

Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

出版信息

Cell Death Dis. 2015 Apr 23;6(4):e1734. doi: 10.1038/cddis.2015.103.

Abstract

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.

摘要

参与组织和维持核结构的基因失调,如SYNE1、SYNE2、TREM43、EMD和LMNA,常常与多种被称为核纤层蛋白病的疾病相关,这些疾病通常会影响肌肉组织。PRR14蛋白最近被报道可将异染色质与核纤层相连,但其功能在很大程度上仍不清楚。在此,我们提供了几条证据,证明PRR14在成肌细胞分化调控中起关键作用。我们发现Prr14在骨骼肌生成过程中表达上调。敲低Prr14会阻碍C2C12分化,而PRR14的过表达则会增强C2C12分化。PRR14的促肌生成活性似乎与其支持细胞存活以及维持核纤层蛋白A/C的稳定性和结构的能力相关。此外,PRR14通过与异染色质蛋白1α(HP1α)结合来刺激MyoD的活性。这些结果共同支持了一个模型,即PRR14通过支持核纤层结构和增强MyoD的活性来促进骨骼肌生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d6a/4650536/3ce2eacda69d/cddis2015103f1.jpg

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