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.
Lichtlen
P
P
Institute of Molecular Biology, University of Zurich, Switzerland.
Schaffner
W
W
D000818:Animals; D004268:DNA-Binding Proteins; D006801:Humans; D019216:Metals, Heavy / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000097809:Transcription Factor MTF-1
D004268:DNA-Binding Proteins; D019216:Metals, Heavy; D015534:Trans-Activators; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1