Putting its fingers on stressful situations: the heavy metal-regulatory transcription factor MTF-1

It has been suggested that metallothioneins, discovered about 45 years ago, play a central role in heavy metal metabolism and detoxification, and in the management of various forms of stress. The metal-regulatory transcription factor-1 (MTF-1) was shown to be essential for basal and heavy metal-induced transcription of the stress-responsive metallothionein-I and metallothionein-II. Recently it has become obvious that MTF-1 has further roles in the transcriptional regulation of genes induced by various stressors and might even contribute to some aspects of malignant cell growth. Furthermore, MTF-1 is an essential gene, as mice null-mutant for MTF-1 die in utero due to liver degeneration. We describe here the state of knowledge on the complex activation of MTF-1, and propose a model with MTF-1 as an interconnected cellular stress-sensor protein involved in heavy metal metabolism, hepatocyte differentiation and detoxification of toxic agents.