Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases
Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases
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DOI：
10.1073/pnas.080064097
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Lu, JR;McKinsey, TA;Olson, EN
肌细胞增强因子-2（MEF 2）转录因子控制肌肉特异性和生长因子诱导基因。我们发现，心肌细胞的肥大性生长在苯肾上腺素和血清伴随着MEF 2的激活，通过翻译后机制介导的钙，钙调蛋白依赖性蛋白激酶（CaMK），和丝裂原活化蛋白激酶（MAPK）信号。CaMK通过从DNA结合结构域解离II类组蛋白脱乙酰酶（HDAC）来刺激MEF 2活性。MAPK通过磷酸化转录激活结构域激活MEF 2，仅当HDAC的抑制通过CaMK信号传导至DNA结合结构域而解除时，MAPK才最大限度地刺激MEF 2活性。这些发现将MEF 2确定为心肌细胞肥大刺激的终点，并证明MEF 2通过HDAC的信号依赖性解离介导对CaMK和MAPK信号通路的协同转录应答。
Myocyte enhancer factor-2 (MEF2) transcription factors control muscle-specific and growth factor-inducible genes. We show that hypertrophic growth of cardiomyocytes in response to phenylephrine and serum is accompanied by activation of MEF2 through a posttranslational mechanism mediated by calcium, calmodulin-dependent protein kinase (CaMK), and mitogen-activated protein kinase (MAPK) signaling. CaMK stimulates MEF2 activity by dissociating class II histone deacetylases (HDACs) from the DNA-binding domain. MAPKs, which activate MEF2 by phosphorylation of the transcription activation domain, maximally stimulate MEF2 activity only when repression by HDACs is relieved by CaMK signaling to the DNA-binding domain. These findings identify MEF2 as an endpoint for hypertrophic stimuli in cardiomyocytes and demonstrate that MEF2 mediates synergistic transcriptional responses to the CaMK and MAPK signaling pathways by signal-dependent dissociation from HDACs.