کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1937179 | 1050710 | 2007 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 1,2-Naphthoquinone disrupts the function of cAMP response element-binding protein through covalent modification 1,2-Naphthoquinone disrupts the function of cAMP response element-binding protein through covalent modification](/preview/png/1937179.png)
1,2-Naphthoquinone (1,2-NQ) is an atmospheric contaminant with electrophilic properties that allow it to react readily with protein thiol groups such as those found on the cAMP response element-binding protein (CREB), a transcription factor with conserved cysteine residues that regulate DNA binding. In the present study, we explored the possibility that the interaction of 1,2-NQ with CREB will affect its activity, resulting in down-regulation of gene expression. With bovine aortic endothelial cells (BAECs) and a cell-free system, 1,2-NQ was found to covalently bind to CREB, and inhibit its DNA binding activity under conditions that were blocked by dithiothreitol. CRE-dependent luciferase activity and the down-regulation of Bcl-2 expression were suppressed by exposure of BAECs to 1,2-NQ. This phenomenon was not seen with the hydrocarbon, naphthalene, which lacks any electrophilic properties. The results indicate that CREB is a molecular target for 1,2-NQ which through irreversible binding, inhibits the function of this transcription factor.
Journal: Biochemical and Biophysical Research Communications - Volume 361, Issue 1, 14 September 2007, Pages 243–248