Differential regulation of D2 receptor gene expression by transcription factor AP-1 in cultured cells

Abstract

The role of the transcription factor AP-1 in regulating D2 receptor transcriptional activity was investigated in D2 receptor expressing neuroblastoma cells, NB41A3, and in non-D2 receptor expressing CHO cells. Deletion of a region containing the putative AP-1 binding site resulted in a significant reduction in the activity in CHO cells; while the activity in NB41A3 cells was increased suggesting that the AP-1 site may differentially regulate D2 gene expression in these distinct cell types. However, both cell lines were found to express significant and similar levels of the transcription factors AP-1. Analysis of phosphorylated proteins in each of the cell lines provided evidence that AP-1 is phosphorylated in NB41A3 cells, but not in CHO cells. This result suggests that differential regulation of D2 gene expression may be related to AP-1 phosphorylation.

Isolation of dopamine D2 receptor (D2R) promoters in Mugil cephalus

“…The intronic sequence 5¢ flanking the first coding exon revealed consensus initiator (Inr) and downstream promoter elements (DPE) as well as putative transcription factor binding sites for AP4, glucoccorticoid receptor (GR), NFkappaB, CREB, AP1, thyroid transcription factor 1 (TTF1), CAAT enhancer binding protein (CEBP), pituitary specific pou domain transcription factor (Pit1, GHF-1), aryl hydrocarbon/Arnt heterodimers (Ahr/Arnt), pituitary homeobox 1 (Ptx1), retinoic acid receptor-related receptor a (RARa), GATA, GC boxes and TATAlike sequences (DQ277010). It also contained elements identical to the enhancers reported in the rat D 2 R promoter (Wang et al 1997). Transient transfection assays of serial deletion constructs from this intronic sequence demonstrated promoter activity in COS-7, aT3 and TE671 cell lines except for the shortest construct, which did not include the putative transcription initiation site (Fig.…”

Antipsychotic‐induced DRD2 upregulation and its prevention by α‐lipoic acid in SH‐SY5Y Neuroblastoma cells

“…Further work will be necessary to understand the underlying mechanisms of AP‐induced DRD2 upregulation and oxidative stress. It has been reported that DRD2 expression is negatively controlled by DA receptor regulating factor (DRRF or KLF16) (Lee et al, 2003) and positively controlled by transcription factors specificity protein 1 (Sp1) and activator protein 1 (AP‐1) (Wang et al, 1997). It has been demonstrated that nuclear factor kappa B (NFκB) has a direct role in DRD2 upregulation by nerve growth factor on prolactinomas (Bontempi et al, 2007; Fiorentini et al, 2002).…”

Cotreatment with the kappa opioid agonist U69593 enhances locomotor sensitization to the D2/D3 dopamine agonist quinpirole and alters dopamine D2 receptor and prodynorphin mRNA expression in rats

“…Understanding these interactions is important to drug development, and these observations may result from interactions at the level of transcriptional regulation. To date, work examining transcriptional regulation of D2R has focused on the sp family of transcription factors, AP-1, and zif 268 (Wang et al 1997;Yajima et al 1998;Takeuchi et al 2002). In addition, a link between these transcription factors and D1R agonists has been established (Nguyen et al 1992;Hope et al 1992Hope et al , 1994Couceyro et al 1994;Keefe and Gerfen 1995;Wang et al 1995;Wang and Mcginty 1995a, b;Turgeon et al 1997;Hope 1998;Zhang et al 2005;Milanovic et al 2006;Radwanska et al 2006).…”