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首页> 外文期刊>Cell cycle >Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition
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Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition

机译：依赖磷酸化的MEF2C降解有助于调节G2 / M过渡

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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 alpha 1 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 (14-3-3 gamma, 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.
机译：心肌细胞增强因子2C（MEF2C）转录因子在骨骼肌分化中起关键作用，促进肌肉特异性基因转录。在这里，我们报告说，在增殖细胞中，MEF2C在有丝分裂中被后期促进复合物/ Cyclosome（APC / C）降解，并且这种下调对于细胞周期的有效进展是必需的。我们表明，这种降解机理要求在MEF2C上存在D-box（R-X-X-L）和2个磷酸基序pSer98和pSer110。 D-box和pSer110基序均由无处不在的替代性alpha 1外显子编码。这两个域介导了MEF2C和CDC20（APC / C的共同激活剂）之间的相互作用。我们进一步报道在成肌细胞中，MEF2C调节G2 / M检查点基因（14-3-3γ，Gadd45b和p21）的表达以及CYCLIN B1的亚细胞定位。观察到MEF2C表达的调节会影响结肠癌细胞的增殖速度，这加强了在细胞周期中控制MEF2C水平的重要性。我们的发现表明，除了作为促肌原性转录因子的公认角色外，MEF2C还可以充当细胞增殖的调节剂。

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