Extracellular signal-regulated kinase 1/2-mediated phosphorylation of p300 enhances myosin heavy chain I/beta gene expression via acetylation of nuclear factor of activated T cells c1.
Extracellular signal-regulated kinase 1/2-mediated phosphorylation of p300 enhances myosin heavy chain I/beta gene expression via acetylation of nuclear factor of activated T cells c1.
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DOI：
10.1093/nar/gkr162
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发表时间：
2011-08
影响因子：
14.9
通讯作者：
Scheibe RJ
中科院分区：
文献类型：
--
作者：
Meissner JD;Freund R;Krone D;Umeda PK;Chang KC;Gros G;Scheibe RJ
活化T细胞核因子（NFAT）c1已被证明是骨骼肌纤维类型转化过程中肌球蛋白重链（MyHC）I/β表达的Ca 2+依赖性上调所必需的。在这里，我们报告激活细胞外信号调节激酶（ERK）12在钙离子载体处理的C2 C12肌管和电刺激比目鱼肌。活化的ERK 1/2增强了NFATc 1依赖性的-2.4 kb MyHCI/β启动子上调，而不影响内源性NFATc 1的亚细胞定位。相反，ERK 1/2增强了转录辅激活因子p300的磷酸化，促进了其向NFATc 1的募集，并增加了NFATc 1-DNA与MyHCI/β启动子的NFAT位点的结合。与此同时，ERK 1/2信号的抑制消除了p300的作用。野生型p300和乙酰转移酶缺陷型突变体（p300 DY）之间的比较表明，增加NFATc 1-DNA结合作为p300介导的NFATc 1乙酰化的结果。p300对MyHCI/β启动子的激活依赖于NFATc 1中两个保守的乙酰化位点，这两个位点影响DNA结合和转录刺激。NFATc 1乙酰化发生在Ca 2 +-离子载体处理的C2 C12肌管或电刺激比目鱼肌。最后，C2 C12肌管中的内源性MyHCI/β基因表达被p300 DY和ERK磷酸化位点缺陷的突变体强烈抑制。总之，ERK 1/2介导的p300磷酸化对于通过乙酰化增强NFATc 1反式激活功能至关重要，这对于Ca 2+诱导的MyHCI/β表达是必需的。
The nuclear factor of activated T-cells (NFAT) c1 has been shown to be essential for Ca2+-dependent upregulation of myosin heavy chain (MyHC) I/β expression during skeletal muscle fiber type transformation. Here, we report activation of extracellular signal-regulated kinase (ERK) 1/2 in Ca2+-ionophore-treated C2C12 myotubes and electrostimulated soleus muscle. Activated ERK1/2 enhanced NFATc1-dependent upregulation of a −2.4 kb MyHCI/β promoter construct without affecting subcellular localization of endogenous NFATc1. Instead, ERK1/2-augmented phosphorylation of transcriptional coactivator p300, promoted its recruitment to NFATc1 and increased NFATc1–DNA binding to a NFAT site of the MyHCI/β promoter. In line, inhibition of ERK1/2 signaling abolished the effects of p300. Comparison between wild-type p300 and an acetyltransferase-deficient mutant (p300DY) indicated increased NFATc1–DNA binding as a consequence of p300-mediated acetylation of NFATc1. Activation of the MyHCI/β promoter by p300 depends on two conserved acetylation sites in NFATc1, which affect DNA binding and transcriptional stimulation. NFATc1 acetylation occurred in Ca2+-ionophore treated C2C12 myotubes or electrostimulated soleus. Finally, endogenous MyHCI/β gene expression in C2C12 myotubes was strongly inhibited by p300DY and a mutant deficient in ERK phosphorylation sites. In conclusion, ERK1/2-mediated phosphorylation of p300 is crucial for enhancing NFATc1 transactivation function by acetylation, which is essential for Ca2+-induced MyHCI/β expression.
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影响因子：
3.9
作者：
Goldspink, G
通讯作者：
Goldspink, G
影响因子：
4.8
作者：
Gusterson, R;Brar, B;Latchman, D
通讯作者：
Latchman, D
影响因子：
4.8
作者：
Chen, Yun-Ju;Wang, Ying-Nai;Chang, Wen-Chang
通讯作者：
Chang, Wen-Chang
DOI：
10.1073/pnas.0812911106
发表时间：
2009-08-11
影响因子：
11.1
作者：
Calabria, Elisa;Ciciliot, Stefano;Murgia, Marta
通讯作者：
Murgia, Marta
DOI：
10.1083/jcb.151.3.663
发表时间：
2000-10-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dunn SE;Chin ER;Michel RN
通讯作者：
Michel RN