Badodi Sara, Baruffaldi Fiorenza, Ganassi Massimo, Battini Renata, Molinari Susanna
a Dipartimento di Scienze della Vita ; Università di Modena e Reggio Emilia ; Modena , Italy.
Cell Cycle. 2015;14(10):1517-28. doi: 10.1080/15384101.2015.1026519.
The Myocyte Enhancer Factor 2C (MEF2C) transcription factor plays a critical role in skeletal muscle differentiation, promoting muscle-specific gene transcription. Here we report that in proliferating cells MEF2C is degraded in mitosis by the Anaphase Promoting Complex/Cyclosome (APC/C) and that this downregulation is necessary for an efficient progression of the cell cycle. We show that this mechanism of degradation requires the presence on MEF2C of a D-box (R-X-X-L) and 2 phospho-motifs, pSer98 and pSer110. Both the D-box and pSer110 motifs are encoded by the ubiquitous alternate α1 exon. These two domains mediate the interaction between MEF2C and CDC20, a co-activator of APC/C. We further report that in myoblasts, MEF2C regulates the expression of G2/M checkpoint genes (14-3-3γ, Gadd45b and p21) and the sub-cellular localization of CYCLIN B1. The importance of controlling MEF2C levels during the cell cycle is reinforced by the observation that modulation of its expression affects the proliferation rate of colon cancer cells. Our findings show that beside the well-established role as pro-myogenic transcription factor, MEF2C can also function as a regulator of cell proliferation.
肌细胞增强因子2C（MEF2C）转录因子在骨骼肌分化过程中发挥关键作用，促进肌肉特异性基因转录。在此我们报告，在增殖细胞中，MEF2C在有丝分裂期被后期促进复合物/细胞周期体（APC/C）降解，并且这种下调对于细胞周期的有效进展是必要的。我们表明，这种降解机制需要MEF2C上存在一个D盒（R-X-X-L）和两个磷酸化基序，即pSer98和pSer110。D盒和pSer110基序均由普遍存在的可变α1外显子编码。这两个结构域介导MEF2C与APC/C的共激活因子CDC20之间的相互作用。我们进一步报告，在成肌细胞中，MEF2C调节G2/M期检查点基因（14-3-3γ、Gadd45b和p21）的表达以及细胞周期蛋白B1的亚细胞定位。细胞周期中控制MEF2C水平的重要性通过以下观察结果得到加强，即其表达的调节会影响结肠癌细胞的增殖速率。我们的研究结果表明，除了作为促肌源性转录因子的既定作用外，MEF2C还可作为细胞增殖的调节因子发挥作用。
