The major interest of
our laboratory is to investigate the biological responses of environmental
stress. The action of heavy metals on the cellular metabolism, signal transduction
and transcriptional regulation are focused. We are currently investigating
the regulation of metallothionein (MT) gene expression under various stresses.
MT is a low molecular weight, cysteine-rich, metal-binding protein that is
synthesized to protect cells against heavy metal toxicity. Upon metal stimulation,
the transcriptional factor of MT gene, metal responsive transcription factor
1 (MTF-1), translocates from cytoplasm to nucleus and binds to metal responsive
element (MRE) at the promoter region to initiate the transcription of MT gene.
We found that MTF-1 is subjected to various post-translational modifications
which may leads to a functional alternation of the transcriptional factor.
We are investigating the molecular mechanism and factors involved in the modifications
to elucidate the physiological roles of the modifications. MTF-1 is an essential
protein that is required for embryonic development of mammals. Our research
may reveal the fine regulatory mechanisms of genes modulated by MTF-1.
Besides the transcriptional regulation of MT gene, we also investigated the mechanism for cadmium-induced necrosis. The target site for a necrosis inhibitor was also analyzed. Taking advantage of the reversible metal-binding characteristics of MT, we were able to develop protein chips to quantify bioavailable metal contents in the aquatic phase. Additionally, nano-sized germanium particles were fabricated to serve as a radiosensitizer. Modifications of the particles are conducted for biomedical applications.