Titre
Functional domains of the heavy metal-responsive transcription regulator MTF-1
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Radtke, F.
Auteure/Auteur
Georgiev, O.
Auteure/Auteur
Muller, H. P.
Auteure/Auteur
Brugnera, E.
Auteure/Auteur
Schaffner, W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0305-1048
Statut éditorial
Publié
Date de publication
1995-06
Volume
23
Numéro
12
Première page
2277
Dernière page/numéro d’article
86
Notes
Journal Article --- Old month value: Jun 25
Résumé
Metallothioneins (MTs) constitute a class of low molecular weight, cysteine-rich, metal binding proteins which are regulated at the level of gene transcription in response to heavy metals and other adverse treatments. We have previously cloned a zinc finger factor (MTF-1) that binds specifically to heavy metal-responsive DNA sequence elements in metallothionein promoters and shown that this factor is essential for basal and heavy metal-induced transcription. Here we report that the C-terminal part of MTF-1 downstream of the DNA binding zinc fingers harbours three different transactivation domains, namely an acidic domain, a proline-rich domain and a domain rich in serine and threonine. When fused to the heterologous DNA binding domain of the yeast factor GAL4 these activation domains function constitutively, i.e. transcription of a GAL4-driven reporter gene is not induced by heavy metals. In search of the region(s) responsible for metal induction, external and internal deletion mutations of mouse and human MTF-1 and chimeric variants thereof were tested with a reporter gene driven by a metal-responsive promoter. The N-terminal part of MTF-1 containing the zinc fingers, which are dependent on zinc for efficient DNA binding, can indeed confer a limited (3- to 4-fold) zinc-responsive transcription when fused to the heterologous activation domain of the viral VP16 protein. Another region containing the acidic and proline-rich activation domains also contributes to metal inducibility, but only in the context of intact MTF-1. This indicates that the activity of MTF-1 results from a complex interplay of different functional domains.
Sujets
PID Serval
serval:BIB_C4277863DC36
PMID
Date de création
2008-01-28T10:39:38.150Z
Date de création dans IRIS
2025-05-20T21:44:08Z