Metallothioneins in Normal and Cancer Cells

Piotr Dziegiel, Bartosz Pula, Christopher Kobierzycki, Mariusz Stasiolek, Marzenna Podhorska-Okolow

Metallothioneins (MTs) are low molecular weight proteins (6-7 kDa), which were detected in almost all types of organisms ranging from prokaryotes to more complex eukaryotic species (Coyle et al. 2002b; Pedersen et al. 2009; Palacios et al. 2011; Vasak and Meloni 2011). In mammals, four main MT isoforms designated from MT-1 to MT-4 were identified (Mididoddi et al. 1996). The MT-1 and MT-2 members of the family were discovered by Margoshes and Vallee in 1957, who first isolated both isoforms from horse renal cortex in search of a cadmium binding protein (Margoshes and Vallee 1957). Then, at the beginning of the 1990s, the MT-3 isoform (also known as GIF-growth inhibitory factor) was extracted from the brain of rats suffering from experimentally induced Alzheimer's disease (Uchida and Tomonaga 1989; Uchida et al. 1991). Following this finding, Quaife et al. discovered the MT-4 isoform in the stratified squamous epithelia of the skin and upper parts of the respiratory tract (Quaife et al. 1994). Most of our knowledge concerning MTs' biology stems from research focusing on the role of MT-1 and MT-2 isoforms (MT-1/2), which are ubiquitously expressed in almost all cells of the body (Davis and Cousins 2000; Krizkova et al. 2009b, 2012; Babula et al. 2012). The functions of MT-3 and MT-4 are currently under intense investigation.