Myocyte enhancer factor 2 (MEF2) tethering to muscle selective A-kinase anchoring protein (mAKAP) is necessary for myogenic differentiation.
Myocyte enhancer factor 2 (MEF2) tethering to muscle selective A-kinase anchoring protein (mAKAP) is necessary for myogenic differentiation.
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肌细胞增强子因子2（MEF2）将肌肉选择性A-激酶锚定蛋白（MAKAP）束缚是肌源性分化所必需的。
DOI：
10.1016/j.cellsig.2012.03.017
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发表时间：
2012-08
影响因子：
4.8
通讯作者：
Dodge-Kafka KL
中科院分区：
文献类型：
--
作者：
Vargas MA;Tirnauer JS;Glidden N;Kapiloff MS;Dodge-Kafka KL
骨骼肌成肌细胞分化为功能性肌管涉及高度调节的转录动力学。肌细胞增强因子2（MEF 2）转录因子对这一过程至关重要，与主调节因子MyoD协同促进肌肉特异性基因转录。MEF 2是广泛的肌源性刺激，转录和post-acetylatically调节，但迄今为止，在了解如何协调MEF 2上游信号产生一致的反应几乎没有进展。在这项研究中，我们定义了一种新的肌肉A激酶锚定蛋白（mAKAP）和MEF 2在骨骼肌之间的相互作用。MEF 2和mAKAP的离散结构域直接结合。利用它们的相互作用来探测mAKAP栓系的MEF 2在肌原性分化期间的功能。MEF 2/mAKAP结合的显性干扰足以在分化的早期阶段阻断MEF 2活化。此外，这种破坏结构域的延长表达有效地阻断了肌源性分化，停止了肌管的形成并降低了几种分化标志物的表达。这项研究扩展了我们对MEF 2在骨骼肌中调控的理解，并确定了mAKAP支架作为MEF 2转录和肌源性分化的促进剂。
Differentiation of skeletal myoblast cells to functional myotubes involves highly regulated transcriptional dynamics. The myocyte enhancer factor 2 (MEF2) transcription factors are critical to this process, synergizing with the master regulator MyoD to promote muscle specific gene transcription. MEF2 is extensively regulated by myogenic stimuli, both transcriptionally and post-translationally, but to date there has been little progress in understanding how signals upstream of MEF2 are coordinated to produce a coherent response. In this study, we define a novel interaction between the muscle A-kinase anchoring protein (mAKAP) and MEF2 in skeletal muscle. Discrete domains of MEF2 and mAKAP bind directly. Their interaction was exploited to probe the function of mAKAP-tethered MEF2 during myogenic differentiation. Dominant interference of MEF2/mAKAP binding was sufficient to block MEF2 activation during the early stages of differentiation. Furthermore, extended expression of this disrupting domain effectively blocked myogenic differentiation, halting the formation of myotubes and decreasing expression of several differentiation markers. This study expands our understanding of the regulation of MEF2 in skeletal muscle and identifies the mAKAP scaffold as a facilitator of MEF2 transcription and myogenic differentiation.
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影响因子：
16
作者：
Michel, JJC;Townley, IK;Scott, JD
通讯作者：
Scott, JD
影响因子：
9.2
作者：
Novitch, BG;Spicer, DB;Lassar, AB
通讯作者：
Lassar, AB
DOI：
10.1073/pnas.260501497
发表时间：
2000-12-19
影响因子：
11.1
作者：
McKinsey, TA;Zhang, CL;Olson, EN
通讯作者：
Olson, EN
影响因子：
64.8
作者：
Dodge-Kafka, KL;Soughayer, J;Scott, JD
通讯作者：
Scott, JD
影响因子：
16
作者：
Lu, JR;McKinsey, TA;Olson, EN
通讯作者：
Olson, EN