Signaling events for metallothionein induction

Metallothioneins (MTs) are low molecular weight, cysteine-rich metal-binding proteins found in a wide variety of organisms including bacteria, fungi and all eukaryotic plant and animal species. They are the single most abundant group of intracellular zinc-binding proteins in eukaryotic cells [Prog. Food Nutr. Sci. 14 (1990) 193]: 5-10% of zinc in human hepatocytes is bound to MTs [Methods Enzymol. 205 (1991) 613; FEBS Lett. 39 (1974) 229]. A critical physiological role for MTs has been suggested to encompass control of zinc availability to proteins requiring zinc for activity, but has not been definitively described. Nevertheless, a hallmark of MT gene regulation is their pattern of expression in different cell types and tissues, and their inducibility by a host of chemical and physical agents acting directly or indirectly on multiple cis-acting motifs in the regulatory regions of MT genes [Prog. Nucleic Acid. Res. Mol. Biol., 66 (2001) 357]. The pattern of physical and chemical events regulating basal MT gene transcription, and induction or repression of MT gene activity, provides valuable insight into the potential functions of MTs. In this review, we describe the transcriptional regulatory processes involved in MT gene expression.