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1,2-Naphthoquinone disrupts the function of cAMP response element-binding protein through covalent modification.

Abstract：

: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_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Endo A,Sumi D,Kumagai Y

doi

10.1016/j.bbrc.2007.07.024

subject

Has Abstract

pub_date

2007-09-14 00:00:00

pages

243-8

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)01485-4

journal_volume

361

pub_type

杂志文章

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