Retinoid X receptor a acts as alpha negative regulator in Nurr1-induced dopaminergic differentiation in rat neural precursor cells

作者：Yoon Eun Hye; Lee Kuem Ju; Kim Yong Seok; Chang Mi Sook; Lee Sang Hun; Park Chang Hwan^*

来源：NeuroReport, 2010, 21(18): 1162-1166.

DOI：10.1097/WNR.0b013e328340ccf9

• dopaminergic differentiation
• Nurr1
• rat embryonic neural precursor cells
• retinoid X receptor alpha

To investigate the role of retinoid X receptor alpha (RXR alpha)-Nurr1 heterodimers in tyrosine hydroxylase (TH) expression, we observed retrovirus-induced RXR alpha-Nurr1 heterodimer interactions with, and transactivation of, the TH promoter region in cultured rat embryonic neural precursor cells. Interestingly, forced expression of RXR alpha with Nurr1 remarkably reduced Nurr1 activity in TH + dopaminergic neuron generation and significantly down-regulated TH promoter activity. These regulatory activities were altered in both Nurr1(dim-) and RXR alpha(dim-) that disrupted dimeric binding, verifying that the Nurr1-RXR alpha heterodimer represses TH promoter activity. Therefore, a plausible explanation for the inhibitory role of RXR alpha in Nurr1-induced TH expression is that RXR alpha differentially affects an inhibitory element of the TH promoter.

• 出版日期2010-12-29