Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea.
Korean J Physiol Pharmacol. 2011 Apr;15(2):95-100. doi: 10.4196/kjpp.2011.15.2.95. Epub 2011 Apr 30.
DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.
DREAM(下游调节元件拮抗调节剂)是一种钙结合蛋白,可调节强啡肽的表达,促进钾通道表面表达,并以表达水平依赖的方式增强早老素加工。然而,目前尚无分子机制可以解释 DREAM 的蛋白水平是如何调节的。在这里,我们确定了 I 组 mGluR(mGluR1/5)是 DREAM 蛋白表达的正调节剂。mGluR1/5 的过表达增加了 DREAM 的细胞水平。DREAM 的上调导致细胞核和细胞质中 DREAM 蛋白增加,其中该蛋白分别作为转录抑制剂和其相互作用蛋白的调节剂。I 组 mGluR 的激动剂 DHPG(3,5-二羟苯甘氨酸)也可上调皮质神经元中的 DREAM 表达。这些结果表明,I 组 mGluR 是第一个被鉴定的可能调节神经元中 DREAM 活性的受体。