Riquelme Cecilia, Barthel Kristen K B, Qin Xiao-Feng, Liu Xuedong
Department of Chemistry and Biochemistry, University of Colorado-Boulder, Boulder, CO 80309, USA.
Exp Cell Res. 2006 Jul 1;312(11):2132-41. doi: 10.1016/j.yexcr.2006.03.016. Epub 2006 Apr 21.
Myogenic differentiation is a fundamental biological process that involves a hierarchical series of events that ultimately leads to muscle-specific gene expression and myofiber formation. Posttranslational modifications of the myogenic regulatory factors have been implicated as important regulatory mechanisms in this process. Here we investigate whether covalent protein modification by a small ubiquitin-like modifier (SUMO) that is known to affect transcription factor activity can impact muscle differentiation. We show that the overall load of sumoylated proteins present in myoblasts diminishes progressively throughout myogenesis. Interestingly, knockdown of the SUMO-conjugating enzyme, Ubc9, severely compromises C2C12 muscle cell terminal differentiation. However, it does not affect the expression, the localization and the activation of MyoD and myogenin. These novel results suggest that protein sumoylation plays a pivotal role in myoblast differentiation and is required to regulate the activity of key targets downstream of MyoD and myogenin.
成肌分化是一个基本的生物学过程，涉及一系列分层级联事件，最终导致肌肉特异性基因表达和肌纤维形成。成肌调节因子的翻译后修饰被认为是这一过程中的重要调节机制。在此，我们研究一种已知会影响转录因子活性的小泛素样修饰物（SUMO）对蛋白质的共价修饰是否会影响肌肉分化。我们发现，在整个成肌过程中，成肌细胞中存在的SUMO化蛋白的总体负荷逐渐减少。有趣的是，SUMO缀合酶Ubc9的敲低严重损害了C2C12肌肉细胞的终末分化。然而，它并不影响MyoD和肌细胞生成素的表达、定位及激活。这些新结果表明，蛋白质SUMO化在成肌细胞分化中起关键作用，并且是调节MyoD和肌细胞生成素下游关键靶点活性所必需的。
