Nuclear localization of metallothionein during cell proliferation and differentiation

Although MT is detected as a cytoplasmic protein in hepatocytes of adult li ver, it can be localized in the hepatocyte nuclei in human fetal liver boun d to zinc and copper. Both nuclear and cytoplasmic localization of MT have been observed in several human tumours, especially in regions of high proli feration, Transient co-localization of zinc and MT has been shown in differ entiating myoblast and 3T3-L1 fibroblasts, and during the G(1)-/S-phase pro gression in cell cycle. Several mechanisms have been proposed for the impor t and retention of MT in the nucleus, including signal transduction pathway s. The high levels of MT in the nucleus of cells under certain conditions m ay be related to the increased requirement for zinc for several metallo-enz ymes 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 r egulate gene expression during certain stages of cell cycle.