Nuclear localization of metallothionein during cell proliferation and differentiation.

Although MT is detected as a cytoplasmic protein in hepatocytes of adult liver, it can be localized in the hepatocyte nuclei in human fetal liver bound to zinc and copper. Both nuclear and cytoplasmic localization of MT have been observed in several human tumours, especially in regions of high proliferation. Transient co-localization of zinc and MT has been shown in differentiating myoblast and 3T3-L1 fibroblasts, and during the G1-/S-phase progression in cell cycle. Several mechanisms have been proposed for the import and retention of MT in the nucleus, including signal transduction pathways. The high levels of MT in the nucleus of cells under certain conditions may be related to the increased requirement for zinc for several metallo-enzymes and transcription factors during rapid growth. The function of nuclear MT may be to protect the cell from DNA damage and apoptosis, and also to regulate gene expression during certain stages of cell cycle.