The "metal transcription factor" MTF-1: biological facts and medical implications.
Metallothioneins (MTs) are a class of small, cysteine-rich proteins that have an important function in heavy metal metabolism and detoxification and in the management of various forms of cell stress. Several lines of evidence suggest a role for metallothioneins in therapy resistance of malignant tumours, regulation of blood pressure and protection against some neurological diseases. Basal and heavy metal-induced expression of the stress-inducible metallothionein-I and -II genes and some other stress-regulated genes depends on the zinc-finger transcription factor MTF-1. MTF-1 acts as a cellular stress-sensor protein and, besides its crucial role in metallothionein expression, is essential for liver development since mice null mutant for MTF-1 die in utero due to hepatocyte degeneration. Under pathological conditions, MTF-1 seems to be involved in clinically important processes such as tumour angiogenesis and drug resistance. It thus seems generally advisable to monitor MTF-1 activity in stress-related processes including aging and carcinogenesis.
Lichtlen
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P
Institut für Molekularbiologie, University of Zurich, Winterthurerstrasse 190, Zürich, CH-8057, Switzerland.
Schaffner
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D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000378:metabolism* / Q000502:physiology; D019216:Metals, Heavy / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018384:Oxidative Stress; D011247:Pregnancy; D011270:Pregnancy, Animal; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000097809:Transcription Factor MTF-1
D004268:DNA-Binding Proteins; D008668:Metallothionein; D019216:Metals, Heavy; D015534:Trans-Activators; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1