Differential regulation of SC1/PRDM4 and PRMT5 mediated protein arginine methylation by the nerve growth factor and the epidermal growth factor in PC12 cells.

Differential regulation of SC1/PRDM4 and PRMT5 mediated protein arginine methylation by the nerve growth factor and the epidermal growth factor in PC12 cells.
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DOI:
10.1016/j.neulet.2013.06.051
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发表时间:
2013-08-29
影响因子:
2.5
通讯作者:
Chittka A
Chittka A
中科院分区:
医学4区
文献类型:
--
作者:
Chittka A

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SC 1/PRMT 5组蛋白甲基转移酶活性被NGF下调,但不被EGF下调。神经生长因子减少核,但不是胞质SC 1/PRMT 5介导的HMTase活性。SC 1和PRMT 5存在于小鼠原代神经元的细胞核和细胞质中。在神经元发育过程中,神经上皮干细胞(NSC)最初经历增殖分裂,随后转换为神经源性细胞,从而产生一个NSC和一个有丝分裂后的神经元。我们最近表明,PRDM转录调节因子家族的成员PRDM 4/SC 1招募II型蛋白质精氨酸甲基转移酶PRMT 5,以维持胚胎小鼠皮质神经干细胞的“干细胞样”细胞状态。然而,鲜为人知的是,这个复杂的增殖或分化诱导生长条件下的活性调节。在目前的工作中,我调查的调节SC 1/PRMT 5介导的甲基化活性与EGF或NGF处理的PC 12细胞。我目前的证据表明,神经生长因子下调SC 1/PRMT 5甲基转移酶(MTase)的活性和SC 1/PRMT 5 MTase活性的减少主要发生在细胞核。我认为高水平的SC 1/PRMT 5活性与细胞的增殖状态有关。
SC1/PRMT5 histone methyltransferase activity is down-regulated by NGF, but not EGF. NGF reduces the nuclear, but not the cytosolic SC1/PRMT5-mediated HMTase activity. SC1 and PRMT5 are found in the nucleus and the cytosol of primary mouse neurons. During neuronal development, the neuroepithelial stem cells (NSCs) initially undergo proliferative divisions, later switching to neurogenic ones whereby one NSC and a post-mitotic neuron are generated. We recently showed that a member of the PRDM family of transcriptional regulators, PRDM4/SC1, recruits a type II protein arginine methyltransferase, PRMT5, to maintain the “stem-like” cellular state of the embryonic mouse cortical NSCs. However, little is known about the regulation of activity of this complex under proliferation- or differentiation-inducing growth conditions. In the present work I investigate the regulation of SC1/PRMT5-mediated methylation activity in PC12 cells treated with EGF or NGF. I present evidence that NGF down-regulates SC1/PRMT5 methyltransferase (MTase) activity and that the reduction in SC1/PRMT5 MTase activity occurs mainly in the nucleus. I suggest that high levels of SC1/PRMT5 activity are associated with the proliferative state of the cells.
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