Signal Tranduction by Copper Ion for Metallothionein Gene Expression

Abstract

Transcription of mammalian metallothionein (MT) genes is activated by a various metals including Zn, Cd, Cu, Hg, Ag and so on. The control sequences located in the 5’-flanking region of MT genes revealed that the short DNA elements, which are called metal responsive elements (MREs) and contain less conserved GC-rich region, mediate metal responsiveness. MREs were initially shown to mediate transcriptional response of MT gene to Zn and Cd, and more recently to oxidative stress. However, the other metals have not shown to be essential for metal-induced transcriptional regulation of MT. In this study, the effect of Cu²⁺ ion to binding of MREs sequences to the nuclear protein from HeLa cells stimulated with TPA (12-O-tetradecanoyl phorbol-13-acetate) was investigated by the gel shift assay, using the plasmid pKB8 which was constructed the human metallothionein (MT)-IIA promoter gene in pUC19.