| Popis: |
Metallothioneins (MTs) are small cysteine-rich proteins that bind transition metal ions such as Cd2+, Zn2+, and Cu+ (metals) (Andrews, 1990; Suzuki et al., 1993; Moffatt and Denizeau, 1997). All vertebrates examined contain two or more distinct MT isoforms which are grouped into four classes, MT-1 through MT-4. MTs have been identified in a wide range of species and are present in various tissues and cell types from yeast to humans. The genes encoding MTs are inducible at the transcriptional level by a wide variety of agents, including metals, hormones, cytokines and reactive oxygen species. Metals are the most general and potent of these inducers. Metal activation of MT gene transcription is dependent on the presence of cfc-acting metal regulatory elements (MREs) which are present in six non-identical copies (MREa through MREf) in the 5′ flanking region of the mouse MT-1gene. The highly conserved MRE core sequence, 5′-TGCRCNC-3′ (R, purine; N, any nucleotide), is necessary and sufficient for induction by metals (Imbert et al., 1990). At least two MREs are required for efficient metal induction and they can be present either in tandem or opposite orientations. In addition, in the mouse MT-1promoter, MREs have different transcriptional efficiencies. MREd is the strongest, MREa and MREc are 50 to 80% weaker, MREb is very weak and MREe and MREf are apparently nonfunctional (Stuart et al., 1985). In addition to MREs, MTgene promoters contain binding sites for the transcription factors Spl, USF/MLTF, AP-1, and AP-2 which contribute to their basal transcriptional efficiency (Imbert et al., 1990). |
