Abstract
Metal responsive transcription factor 1 (MTF-1) regulates the expression of genes involving in metal homeostasis and anti-oxidative stress. MTF-1 locates mainly in cytoplasm. With the stimulation of cadmium or zinc, MTF-1 translocates into nucleus and binds to the promoter of target genes. We found that MTF-1 can also be activated by arsenic (As) treatment and moves into nucleus. Analysis of the cytoplasmic MTF-1 reveals that the protein level decreased with As exposure time. On the other hand, nuclear MTF-1 increased within 1 h of As treatment, but decreased afterward. Image analysis indicates that MTF-1 aggregates in the nucleus and the aggregates trafficked back to cytoplasm with As treatment. Noticeably, As-induced MTF-1 aggregation occurred only when the protein translocated into nucleus. There was no aggregates occurred for the MTF-1 mutants that failed to enter the nucleus with As treatment. Noticeably, the aggregated MTF-1 retained in the nucleus once the nuclear export signal was destructed. Using wild type and PML-null MEF cells to treated with Cd, Zn or As showed that MTIIA expression was dramatically reduced in the PML-null MEF cells. The result indicates that PML is regulated to integral MTF-1 activity. However, whether PML is required for the trafficking of MTF-1 under As stress remains unknown.